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Inflammatory pseudotumor (IPT) is a rare benign tumor of unknown etiology that can occur in almost any organ system. It has neoplastic features such as local recurrence, invasive growth, and vascular invasion, leading to the possibility of malignant sarcomatous changes. The clinical presentations of colonic IPT may include abdominal pain, anemia, a palpable mass, and intestinal obstruction. A few cases of colonic IPT have been reported, but colonic IPT with pedunculated morphology is very rare. Furthermore, since it can mimic malignant polyps, understanding the endoscopic findings of colonic IPT is important for proper treatment. Herein, we present a case of colonic IPT with pseudosarcomatous changes, presenting as a large polyp, mimicking a malignant polyp in the cecum, along with a literature review.

International audience; Invasive growth along white matter (WM) tracts is one of the most prominent clinicopathological features of glioma and is also an important reason for surgical treatment failure in glioma patients. A full understanding of relevant clinical features and mechanisms is of great significance for finding new therapeutic targets and developing new treatment regimens and strategies. Herein, we review the imaging and histological characteristics of glioma patients with WM tracts invasion and summarize the possible molecular mechanism. On this basis, we further discuss the correlation between glioma molecular typing, radiotherapy and tumor treating fields (TTFields) and the invasion of glioma along WM tracts.

Congenital intracranial tumors are rare, accounting for 0.5–1.9% of pediatric tumors. Though antenatal detection rates have improved with ultrasound (US) and MRI, histopathology gives a definite diagnosis. Prognosis is guarded as there is no effective postnatal treatment. We present a fetus incidentally diagnosed with intracranial teratoma by US and MRI at 36 weeks of gestation. Elective cesarean was performed for anticipated labor dystocia. A female baby with head circumference > 99th centile was delivered. Due to the invasive growth potential of the tumor, the baby succumbed at 4 months of palliative care. Further research is required for devising new treatment modalities to tackle this intractable condition.

Background Pituitary adenoma (PA) accounts for 10–15% of all intracranial neoplasms. Despite their benign nature, PA often shows invasive growth. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play important roles in PA initiation and progression. Aim The aim of this study was to find specific profiles of miR-200a and long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in PA based on a comparative study using Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses of tumor tissue and plasma. Methods Plasma and PA tissue samples were obtained from two groups of included patients (15 invasive and 15 non-invasive PA). In addition, plasma samples from patients with invasive PA have collected pre- and post-operation. Plasma and tissue samples subjected to qRT-PCR analyses for the expression levels of miR-200a and lncRNA ANRIL. Results The expression levels of miR-200a and lncRNA ANRIL were increased in tissue samples patients with invasive PA than in the patients with non-invasive PA. In addition, the expression levels of circulating miR-200a and lncRNA ANRIL were increased in patients with invasive PA than in patients with non-invasive PA in the pre-operation period. However, the expression level of plasma circulating miR-200a and lncRNA ANRIL was decreased in patients with invasive PA in the post-operation period. Our results depicted a miR-200a and lncRNA ANRIL expression in tissue and plasma samples in the patients with invasive PA. In addition, Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic value of these circulating miR-200a and lncRNA ANRIL. Conclusion The expression of these tumor-associated ncRNAs has been elevated in the PAs. Therefore, miR-200a and lncRNA ANRIL represents as biomarkers for diagnosis and potential targets for novel invasive PA treatment strategies.

Non-functional pituitary adenomas are a morphologically heterogeneous group and are subdivided into silent adenomas that have immunoreactivity to tropic hormones and are similar in structure to typical adenocytes but do not lead to the development of clinical signs of hormonal hypersecretion (silent gonadal, cortical-, thyroid and mammotropinomas), and tumors that do not have specific markers and are similar to adenohypophyseal cells (zero-cell tumors and oncocytomas). According to the studies conduc­ted, all types of silent adenomas have different biological activity, secretory potential, and postoperative outcomes. Active detection of silent pituitary adenomas during immunohistochemical analysis not only allows identifying patients at high risk of disease recurrence but also developing optimal treatment and follow-up tactics, determining indications and evaluating the feasibility of drug and radiation therapy after a neurosurgical intervention. The review article is devoted to the search for prognostic markers of invasive growth of inactive pituitary adenomas. A high level of Ki-67 can be considered as an independent factor and a marker of poor prognosis in pituitary adenomas. The patients with adenomas with high proliferative activity were more often found to develop invasive growth of the adenoma, as well as its malignant transformation — the development of adenocarcinoma. This marker does not depend on other negative prognostic signs — the age and sex of a patient, the adenoma size. Besides, an increase in the proliferation level is more often observed in somatotropinomas and prolactinomas. In recent years, the concept of the cellular and molecular biology of pituitary tumors has changed significantly. It is known that transcription factors regulate the transformation of progenitor cells into mature secretory cells during embryogenesis. Therefore, the search for prognostic criteria for adenomas continues., Гормонально неактивные аденомы гипофиза представляют собой морфологически гетерогенную группу и подразделяются на «немые» аденомы, которые обладают иммунореактивностью к тропным гормонам и похожи по строению на типичные аденоциты, но не приводят к развитию клинических признаков гормональной гиперсекреции, и опухоли, не имеющие специфических маркеров и сходства с аденогипофизарными клетками (ноль-клеточные опухоли и онкоцитомы). Согласно проводимым исследованиям, все типы «немых» аденом имеют различные биологическую активность, секреторный потенциал и исходы в после­операционном периоде. Активное выявление «немых» аденом гипофиза при проведении иммуногистохимического анализа позволяет не только выявить пациентов из группы высокого риска рецидива заболевания, но и выработать оптимальную тактику лечения и дальнейшего наблюдения, определить показания и оценить целесообразность медикаментозной и лучевой терапии после проведенного нейрохирургического вмешательства. Обзорная статья посвящена вопросам поиска прогностических маркеров инвазивного роста неактивных аденом гипофиза. Высокий уровень Кi-67 может рассматриваться как независимый фактор и маркер неблагоприятного прогноза при аденомах гипофиза. У больных, аденомы которых имеют высокий уровень пролиферативной активности, чаще наблюдается инвазивный рост аденомы, а также ее злокачественное перерождение — развитие аденокарциномы. Этот маркер не зависит от других негативных прогностических признаков — возраста и пола пациента, размера аденомы. Кроме того, повышение уровня пролиферации чаще наблюдается в соматотропиномах и пролактиномах. В последние годы существенно изменилось представление о клеточной и молекулярной биологии опухолей гипофиза. Известно, что транскрипционные факторы регулируют трансформацию клеток-предшественников питуицитов в зрелые секреторные клетки во время эмбриогенеза. Поэтому продолжается поиск прогностических критериев для аденом., Гормонально неактивні аденоми гіпофіза становлять морфологічно гетерогенну групу і поділяються на «німі» аденоми, які мають імунореактивність до тропних гормонів і подібні за будовою до типових аденоцитів, але не призводять до розвитку клінічних ознак гормональної гіперсекреції, і пухлини, що не мають специфічних маркерів і схожості з аденогіпофізарними клітинами (нуль-клітинні пухлини й онкоцитоми). Згідно з проведеними дослідженнями, всі типи «німих» аденом мають різні біологічну активність, секреторний потенціал і результати в післяопераційному періоді. Активне виявлення «німих» аденом гіпофіза при проведенні імуногістохімічного аналізу дозволяє не тільки виявити пацієнтів із групи високого ризику рецидиву захворювання, а й виробити оптимальну тактику лікування і подальшого спостереження, визначити показання та оцінити доцільність медикаментозної і променевої терапії після проведеного нейрохірургічного втручання. Оглядова стаття присвячена питанням пошуку прогностичних маркерів інвазивного росту неактивних аденом гіпофіза. Високий рівень Кі-67 може розглядатися як незалежний фактор і маркер несприятливого прогнозу при аденомах гіпофіза. У хворих, аденоми яких мають високий рівень проліферативної активності, частіше спостерігається інвазивний ріст аденоми, а також її злоякісне переродження — розвиток аденокарциноми. Цей маркер не залежить від інших негативних прогностичних ознак — віку і статі пацієнта, розміру аденоми. Крім того, підвищення рівня проліферації частіше спостерігається в соматотропіномах і пролактиномах. Останнім часом істотно змінилося уявлення про клітинну та молекулярну біологію пухлин гіпофіза. Відомо, що транскрипційні фактори регулюють трансформацію клітин-попередників пітуїцитів у зрілі секреторні клітини під час ембріогенезу. Тому триває пошук прогностичних критеріїв для аденом.

Purpose Most HER2 positive invasive cancers are either intrinsic non-responsive or develop resistance when treated with 1st line HER2 targeting drugs. Both 1st and 2nd line treatments of HER2 positive cancers are aimed at targeting the HER2 receptor directly, thereby strongly limiting the treatment options of HER2/ErbB2 inhibition resistant invasive cancers. Methods We used phenotypic high throughput microscopy screening to identify efficient inhibitors of ErbB2-induced invasion using 1st line HER2 inhibitor trastuzumab- and pertuzumab-resistant, p95-ErbB2 expressing breast cancer cells in conjunction with the Prestwick Chemical Library®. The screening entailed a drug’s ability to inhibit ErbB2-induced, invasion-promoting positioning of lysosomes at the cellular periphery, a phenotype that defines their invasiveness. In addition, we used high throughput microscopy and biochemical assays to assess the effects of the drugs on lysosomal membrane permeabilization (LMP) and autophagy, two features connected to cancer treatment. Using 2nd line HER2 inhibitor lapatinib resistant 3-dimensional model systems, we assessed the effects of the drugs on ErbB2 positive breast cancer spheroids and developed a high-throughput invasion assay for HER2 positive ovarian cancer organoids for further evaluation. Results We identified Auranofin, Colchicine, Monensin, Niclosamide, Podophyllotoxin, Quinacrine and Thiostrepton as efficient inhibitors of invasive growth of 2nd line HER2 inhibitor lapatinib resistant breast cancer spheroids and ovarian cancer organoids. We classified these drugs into four groups based on their ability to target lysosomes by inducing autophagy and/or LMP, i.e., drugs inducing early LMP, early autophagy with late LMP, late LMP, or neither. Conclusions Our results indicate that targetable lysosome-engaging cellular pathways downstream of ErbB2 contribute to invasion. They support lysosomal trafficking as an attractive target for therapy aiming at preventing the spreading of cancer cells. Since these drugs additionally possess anti-inflammatory activities, they could serve as multipurpose drugs simultaneously targeting infection/inflammation and cancer spreading.

Summary This report documents the clinicopathological features of cutaneous chromatophoromas in four wild-caught, captive Australian elapid snakes: a strap-snouted brown snake (Pseudonaja aspidoryncha), a tiger snake (Notechis scutatus), an Eastern brown snake (Pseudonaja textilis) and a Mengden’s brown snake (Pseudonaja mengdeni). All tumours were subclassified as melanophoromas, with three assessed as malignant on the basis of invasive growth or presence of intracoelomic metastases. The chromatophoromas were single or multiple, black or orange pigmented, cutaneous, sometimes ulcerated, plaques or nodules. Microscopically, the neoplastic cells were often spindle shaped with low or variable pigmentation. Neoplastic cells in one tumour were notable for their pleomorphic round cell morphology and high mitotic rate. One snake with late-stage metastasis survived for over 5 years. There are few reports of chromatophoromas in elapid snakes and, to our knowledge, this is the first report of these tumours in Australian elapid snakes.

Background Sixty percent of surgically resected brain metastases (BrM) recur within 1 year. These recurrences have long been thought to result from the dispersion of cancer cells during surgery. We tested the alternative hypothesis that invasion of cancer cells into the adjacent brain plays a significant role in local recurrence and shortened overall survival. Methods We determined the invasion pattern of 164 surgically resected BrM and correlated with local recurrence and overall survival. We performed single-cell RNA sequencing (scRNAseq) of >15,000 cells from BrM and adjacent brain tissue. Validation of targets was performed with a novel cohort of BrM patient-derived xenografts (PDX) and patient tissues. Results We demonstrate that invasion of metastatic cancer cells into the adjacent brain is associated with local recurrence and shortened overall survival. scRNAseq of paired tumor and adjacent brain samples confirmed the existence of invasive cancer cells in the tumor-adjacent brain. Analysis of these cells identified cold-inducible RNA-binding protein (CIRBP) overexpression in invasive cancer cells compared to cancer cells located within the metastases. Applying PDX models that recapitulate the invasion pattern observed in patients, we show that CIRBP is overexpressed in highly invasive BrM and is required for efficient invasive growth in the brain. Conclusions These data demonstrate peritumoral invasion as a driver of treatment failure in BrM that is functionally mediated by CIRBP. These findings improve our understanding of the biology underlying postoperative treatment failure and lay the groundwork for rational clinical trial development based upon invasion pattern in surgically resected BrM.

Adenoid cystic carcinoma (ACC) is a relatively rare epithelial malignant tumor of the major and minor salivary glands with deceptive benign histologic appearance characterized by indolent, locally invasive growth with a high propensity for local recurrence and distant metastasis. Typical ACC has a cribriform pattern, presenting a very aggressive course among the histologic variants. According to the Armed Forces Institute of Pathology (AFIP), ACC was considered the fifth most common malignant epithelial tumor of the salivary gland. ACC is more common in the minor salivary gland, the palate being the most common site, submandibular salivary gland and least followed by sublingual and parotid glands. ACC accounts for about 1% of all malignant tumors of the oral and maxillofacial regions. Thus, considering its rarity, we would like to discuss a case report of ACC of the submandibular salivary gland in a 52-year-old female patient with a typical histological pattern, which would epitomize all cases of ACC along with extensive management.

Purpose. Nonfunctioning gonadotropic pituitary neuroendocrine tumors (PitNETs) are among the most frequent neoplasms of pituitary gland. Although PitNETs are commonly considered benign, a notable part of patients suffer from tumor recurrence after treatment. Invasive growth of pituitary tumor is among the most important prognostic factors. Since molecular features of invasiveness are of potential clinical usefulness, this study was aimed to verify whether invasive and noninvasive nonfunctioning gonadotropic PitNETs differ in the miRNA expression profile and whether the differences could provide a possible molecular classifier. Methods. miRNA profiles were determined in 20 patients (11 invasive and 9 noninvasive tumors) using next-generation sequencing. The expression of selected miRNAs was assessed in the independent cohort of 80 patients with qRT-PCR. Results. When miRNA profiles of invasive and noninvasive tumors were compared, 29 miRNAs were found differentially expressed. Hsa-miR-184, hsa-miR-181a-2-3p, hsa-miR-93-3p, hsa-miR-574-5p, hsa-miR-185-5p, and hsa-miR-3200-5p showed a potential clinical value according to ROC curve analysis. Unfortunately, differential expression of only hsa-miR-185-5p was confirmed in the validation cohort, with AUG at 0.654. Conclusion. Differences in miRNAs expression profiles in invasive and noninvasive gonadotropic PitNETs are slight and the level of miRNA expression seems not to be applicable as useful classifier of tumor invasiveness.

Angiomyxoma is a rare benign tumor prone to aggressive and invasive growth and relapse. Very few case reports of tumors with this morphology have been published in the world literature. In this paper, we report a rare case of penile angiomyxoma, which illustrates that any preoperative examination does not allow physicians to suspect this tumor type. This fact makes physicians be alert for cancer and use the active surgical tactics even if a tumor is supposed to be benign.

ERK/MAPK signal transduction pathway participates in occurrence and progression of breast cancer. This study utilized epidermal growth factor (EGF) and ERK antagonist PD98059 to analyze ERK/MAPK signal's role in breast cancer cells. Breast cancer MCF-7 cell line was separated into control group, EGF group, PD98059 group and EGF+ PD98059 group. Cell proliferation activity was assessed by MTT, whilst TUNEL was to describe cell apoptosis. Transwell assay was employed for cell invasion and migration. Protein expression of ERK1/2 and p-ERK1/2. Compared to control group, EGF treatment elevated cell proliferation or invasion/migration and decreased apoptosis at 6 h, 12 h and 24 h. PD98059 treatment decreased proliferation activity or cell invasion/migration, and enhanced apoptosis. Treatment of EGF plus PD98059 further decreased proliferation and invasion/migration compared to EGF group, but with higher level than PD98059 group (p < 0 05). EGF treatment elevated ERK1/2 and pERK1/2, PD98059 group had lower ERK1/2 or pERK1/2 expression, whilst EGF plus PD98059 treatment further decreased ERK1/2 and pERK1/2 expression (p < 0 05). EGF can regulate proliferation and invasion of breast cancer MCF-7 cells via ERK/MAPK signaling.

Cancer is a life-threatening disease that has plagued humans for centuries. The vast majority of cancer-related mortality results from metastasis. Indeed, the invasive growth of metastatic cancer cells in vital organs causes fatal organ dysfunction, but metastasis-related deaths also result from cachexia, a debilitating wasting syndrome characterized by an involuntary loss of skeletal muscle mass and function. In fact, about 80% of metastatic cancer patients suffer from cachexia, which often renders them too weak to tolerate standard doses of anticancer therapies and makes them susceptible to death from cardiac and respiratory failure. The goals of this review are to highlight important findings that help explain how cancer-induced systemic changes drive the development of cachexia and to discuss unmet challenges and potential therapeutic strategies targeting cachexia to improve the quality of life and survival of cancer patients.

High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG. Funding Agency Brain Tumour Research Ollie Young Foundation Portuguese Foundation for Science and Technology IF/00614/2014 FCT exploratory grant IF/00614/2014/CP12340006 FCT Research Center Grant UID/BIM/04773/2013CBMR1334 info:eu-repo/semantics/publishedVersion

Amaç:Rektal kanserler (RK) batı dünyasında en sık görülenkanserlerden biridir. RK için en önemli prediktif gösterge TNMsistemidir. Bununla birlikte, aynı tümör evresi ile karakterizeedilen hastalar sıklıkla belirgin farklı sağ kalımlara sahiptir.Bu araştırmada, stage III RK’larda İnvasiv büyüme paterni(İBP) ve Tümör nekrozu (TN)’nun hayatta kalmaya etkisini analizettik.Gereçve Yöntemler: 1999-2012 yılları arasında KırıkkaleÜniversite’sinde stage III RK nedeniyle opere olan yüzkırk beşhasta bu çalışmaya dahil edildi. Bu parametreler hematoksilen veeozin boyalı kesitlerde skorlandı. Sonuçlar ve klinikopatolojiközellikler arasındaki ilişki analiz edildi.Bulgular:Buparametreler, büyük boyutlu tümör (İBP:p, Aim:Rectal carcinomas(RC) are one of the most common cancers in the western world. TNMsystem is themost significant predictive indicator in these tumors butpatients characterized by the same stage often have prominentdistinct survival. Inthis research, we analyzed the survival effect ofInvasive growth pattern (IGP) and Tumor necrosis (TN) instage III RC.Materialand Methods:A hundred forty-fivepatients operated for stage III RCduring 1999-2012 at Kırıkkale University were included in thisresearch. These parameters were scored on hematoxylinand eosin stained sections.Therelationship between the results and the clinicopathologicalcharacteristics was analyzed.Results:Theseparameters were significantly upregulated in RCs which classified ashighertumorsize (IGP: p

More than 80% of primary lung cancers are non-small cell lung carcinomas (NSCLCs), with adenocarcinoma the most common histologic subtype of NSCLC. Diagnosis of NSCLC is primarily made by histologic assessment, which also informs treatment selection (1). Lung adenocarcinoma is well-known to be histologically heterogenous, as reflected in the 4th edition of the World Health Organization classification, which recommends the use of histologic subtyping in 5% increments. The five major histologic subtypes are lepidic, acinar, papillary, micropapillary, and solid (1). Predominant subtype is predictive of clinical behavior: lepidic is regarded as low-risk, acinar and papillary as intermediate-risk, and micropapillary and solid as high-risk (2). Ground glass opacity (GGO) on computed tomography (CT) has been shown to be associated with lepidic growth and consolidation is associated with invasive growth.

Basal cell carcinoma (BCC) is characterized by slow but locally invasive growth. Although there is low metastatic potential, if not treated early, these skin cancers can lead to significant morbidity and mortality. In this case report, we present a man with a neglected BCC that developed into what is termed a giant BCC or one that is greater than 5 cm. This tumor was discovered only upon workup of orthostatic lightheadedness and iron deficiency anemia. Although rare, basal cell carcinoma must be included on the differential of a large cutaneous lesion and may be a source of significant blood loss.

Mammary solid papillary carcinoma and usual duct hyperplasia (UDH) of the breast are morphological look-alikes, characterized by cellular streaming, solid growth, and a lack of high-grade nuclear atypia. Here, we report a challenging papillary lesion in the breast of a 48-year-old woman that presented with a double pitfall. A core needle biopsy showed a solid papillary proliferation of epithelial cells with oval to round overlapping nuclei, surrounded by a sclerotic stroma. This distorted lesion contained peripheral clefts and cellular streaming, without high-grade nuclear atypia. Immunohistochemistry showed diffuse heterogenous immunoreactivity for estrogen receptor and cytokeratin 5, and no immunoreactivity for chromogranin and synaptophysin. The immunohistochemical profile distinguished this sclerosed papilloma with extensive UDH from a solid papillary carcinoma. The lumpectomy specimen revealed a second challenge, where multiple epithelial islets without surrounding myoepithelial cells were observed near the papilloma, mimicking an invasive carcinoma. These islets displayed the same immunohistochemical profile as the sclerosed papilloma and they were surrounded by steatonecrosis and reactive fibroblasts, indicating epithelial displacement within the biopsy needle tract. A sclerosed papilloma with extensive UDH is a morphologically challenging mimic of a solid papillary carcinoma. Immunohistochemistry is helpful to distinguish both entities from one another. Extensive epithelial displacement in the biopsy tract made this case particularly challenging, as the displaced epithelial islets mimicked an invasive carcinoma. Pathologists should be aware of this uncommon double pitfall to prevent misdiagnosis.

Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary tumors. Methods: We investigated LINE-1 methylation levels in 80 tumors and normal pituitary glands with bisulfite-pyrosequencing. Expression of two LINE-1 open reading frames (L1-ORF1 and L1-ORF2) was analyzed with qRT-PCR in tumor samples and mouse gonadotroph pituitary cells treated with DNA methyltransferase inhibitor. Immunohistochemical staining against L1-ORF1p was also performed in normal pituitary glands and tumors. Results: Hypomethylation of LINE-1 was observed in pituitary tumors. Tumors characterized by invasive growth revealed lower LINE-1 methylation level than noninvasive ones. LINE-1 methylation correlated with overall DNA methylation assessed with HM450K arrays and negatively correlated with L1-ORF1 and L1-ORF2 expression. Treatment of αT3-1 gonadotroph cells with 5-Azacytidine clearly increased the level of L1-ORF1 and L1-ORF2 mRNA, however, its effect on LβT2 cells was less pronounced. Immunoreactivity against L1-ORF1p was higher in tumors than normal tissue. No difference in L1-ORF1p expression was observed in invasive and noninvasive tumors. Conclusion: Hypomethylation of LINE-1 is related to invasive growth and influences transcriptional activity of transposable elements.

Carcinoma cuniculatum (CC) is a rare clinicopathologic variant of squamous cell carcinoma. Histologically, it is characterized by invasive growth of bland, acanthotic, and keratinizing squamous epithelium that forms multiple rabbit burrow-like, keratin-filled crypts and sinuses. We present a 51-year-old male smoker with CC of the left vocal cord. The tumor was staged T1a and the patient was disease-free 12 months after surgery. To our knowledge, this is the fourth case of CC of the larynx reported in the English literature and the first, due to its early diagnosis, where radical surgery was not performed. We highlight the necessity for awareness of this entity and coordination between otolaryngologists, radiologists, and pathologists for early diagnosis and organ-sparing surgical treatment.

Background There are ongoing studies to predetermine non-functional invasive pituitary adenomas which may show aggressive behavior. Our aim is to discuss whether there is a relationship between the immunohistochemical presence of GH, FSH, LH, PRL, ACTH, TSH and their aggressive clinical course in non-functional pituitary adenomas. Materials and Methods In this study, we evaluated retrospectively the files of the patients who were diagnosed with thesellar or parasellar tumor in our endocrinology clinic between the years of 2004-2014.The patients were divided into two groups as non-invasive pituitary adenomas and non-functional invasive pituitary adenomas. The immunohistochemical staining characteristics were compared between the two groups. Results In this study, we scanned the data of 70 patients who were followed for non-functional sellar or parasellar mass. 47.1% of the patients were female and 52.9% of the patients were male.39 patients had a non-functional pituitary adenoma.The rate of non-functional invasive adenoma was found to be 20.5%. There was a significant relationship between the immunohistochemical positivity of GH, FSH, LH andaggressive behavior of non-functional invasive adenomas. There was no a significant relationship between the immunohistochemicalpositivityof PRL, ACTH, TSH and aggressive behavior of non-functional invasive adenomas. Conclusion We found silent GH and gonadotropin adenomas as non-functional aggressive pituitary adenoma. More aggressive treatment and close clinical monitoring should be performed because atypical pituitary adenomas are characterized by invasive growth and aggressive clinical course.

Objectives The eighth edition of the American Joint Committee on Cancer staging manual now stratifies nonmucinous lung adenocarcinomas (nmLACAs) by the size of the invasive component only. This is determined by direct gross or microscopic measurement; however, a calculated invasive size based on the percentage of invasive growth patterns has been proposed as an alternative option. Methods To compare radiologic with different pathologic assessments of invasive tumor size, we retrospectively reviewed a cohort of resected nmLACAs with a part-solid appearance on computed tomography (CT) scan (n = 112). Results The median direct microscopic pathologic invasive measurements were not significantly different from the median calculated pathologic invasive measurements; however, the median CT invasive measurements were 0.26 cm larger than the median direct pathologic measurements (P < .001). Conclusions Our results show that pathologic calculated invasive tumor measurements are comparable to direct microscopic measurements of invasive tumor, thereby supporting the recommendation for use of calculated invasive tumor size by the pathologist if necessary.

Background Pituitary adenomas (PAs) are among the most common brain tumors which characteristically become symptomatic due to the mass effect on surrounding structures and/or hormonal imbalances. This study describes 28 cases of PAs with an extrasellar invasive growth (EIG) at the early stage of tumor growth with normal sellar cavity size. Methods 1200 cases of PAs either treated medically or via Endoscopic transsphenoidal surgery were reviewed during a 10-year period. Pre-operative imaging was analyzed to evaluate the tumor expansion pattern, tumor invasion sites and other relevant tumor properties. A comprehensive preoperative endocrinological along with postoperative histopathological studies were conducted to evaluate the subjects’ homeostasis and further identify the lesions characteristics. Results Of the 28 patients, patients 19, 2, 1 and 6 had a growth hormone (GH)-secreting PA, an adrenocorticotropic hormone (ACTH)-secreting PA, a nonfunctional PA (NFPA) and a mix-hormones secreting PA, respectively. There was a statistically significant difference between patients with and without EIG regarding types of PAs (P = 0.000). Post-hoc tests demonstrated that GH-secreting PAs (P = 0.0003) and mix-hormones secreting PAs (P = 0.0000) are significantly more invasive, while NFPAs (P = 0.0000) are less invasive. There was not a statistically significant difference between the invasion sites and different types of PAs (P = 0.122). Conclusion Among different histological subtypes of PAs, GH-secreting PAs revealed a remarkable tendency for EIG with normal sellar cavity size. The extra-sellar tumor extension with a normal sella did not correlate with atypical histology. Considering EIG patterns, surgeons should be vigilant to investigate and follow the tumor spreading to its enclosing boundary during surgery, the clival part of sphenoid bone should be more exposed, and both inferomedial and lateral borders of the sphenoid sinus should be carefully explored in order to remove the tumor.

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer, however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential.

We develop a three-dimensional genuinely hybrid atomistic-continuum model that describes the invasive growth dynamics of individual cancer cells in tissue. The framework explicitly accounts for phenotypic variation by distinguishing between cancer cells of an epithelial-like and a mesenchymal-like phenotype. It also describes mutations between these cell phenotypes in the form of epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET). The model consists of a hybrid system of partial and stochastic differential equations that describe the evolution of epithelial-like and mesenchymal-like cancer cells, respectively, under the consideration of matrix-degrading enzyme concentrations and the extracellular matrix density. With the help of inverse parameter estimation and a sensitivity analysis, this three-dimensional model is then calibrated to an in vitro organotypic invasion assay experiment of oral squamous cell carcinoma cells.

Hypertrophic scarring (HS), a fibroproliferative disorder caused by abnormal wound healing after skin injury, is characterized by excessive deposition of extracellular matrix and invasive growth of fibroblasts. Numerous studies have reported that non-coding RNAs (ncRNAs) including microRNAs (miRNAs, miRs) and long non-coding RNAs (lncRNAs) play important roles in HS formation. Exploring non-coding RNA-based methods to treat scar would be instrumental for devising new effective therapies against scar. J. Cell. Biochem. 118: 1965-1968, 2017. © 2017 Wiley Periodicals, Inc.

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all common cancers. However, divergent outcomes exist between patients, suggesting distinct underlying tumor biology. Here, we delineated this heterogeneity, compared interconnectivity between classification systems, and experimentally addressed the tumor biology that drives poor outcome. RNA-sequencing of 90 resected specimens and unsupervised classification revealed four subgroups associated with distinct outcomes. The worst-prognosis subtype was characterized by mesenchymal gene signatures. Comparative (network) analysis showed high interconnectivity with previously identified classification schemes and high robustness of the mesenchymal subtype. From species-specific transcript analysis of matching patient-derived xenografts we constructed dedicated classifiers for experimental models. Detailed assessments of tumor growth in subtyped experimental models revealed that a highly invasive growth pattern of mesenchymal subtype tumor cells is responsible for its poor outcome. Concluding, by developing a classification system tailored to experimental models, we have uncovered subtype-specific biology that should be further explored to improve treatment of a group of PDAC patients that currently has little therapeutic benefit from surgical treatment.

Targeting metabolic reprogramming has emerged as a promising strategy for therapeutic intervention in cancer. We identify that fatty acid synthase (FASN) is essential for cancer initiation playing a critical role in acquiring three-dimensional (3D) growth properties during transformation. In vivo inhibition of FASN before oncogenic activation prevents tumor development and invasive growth suggesting that FASN could be a potential target for cancer prevention.

The historical descriptions of glial tumors are often poorly understood and interpreted. The gross and histological depictions of glial tumors are often credited to Virchow, and while the first true histological description is truly his, gross descriptions can be traced back to the beginning of the 1800s, with their classification and histogenesis attributed to Percival Bailey and Harvey Cushing. Without any question, the most prominent and under-credited researcher in the field of glioma pathobiology was the German neuropathologist Hans Joachim Scherer. Despite the limited armamentarium available to him, his systematic approach led to conclusions, some of which have now been molecularly explained today while some are still being widely researched. Scherer defined pseudopalisadic necrosis as a pathognomonic feature of glioblastoma multiforme (GBM), as well as secondary features due to tumor growth, known collectively as secondary Scherer figures, for example, neuronal and vascular satellitosis, tract and subpial aggregation. All these features are key points in the modern histological diagnosis of glial tumors. Other contributions by Scherer include the definition of glomeruloid vascular proliferation and his conclusion that they are caused by vascular factors released by the tumor, decades before vascular endothelial growth factor and its receptors were discovered and their role in glioma evolution was established. Furthermore, he concluded that GBMs can arise de novo (primary) or from a preceding lower-grade glioma (secondary). All his contributions find their place in all modern aspects of glioma research, with some giving a simple explanation of the phenomena observed in glial tumors.

OBJECTIVE. The purpose of this study was to explore the value of FDG PET combined with high-resolution CT (HRCT) in predicting the pathologic subtypes and growth patterns of early lung adenocarcinoma. MATERIALS AND METHODS. A retrospective analysis was conducted on the PET/CT data on ground-glass nodules (GGNs) resected from patients with stage IA lung adenocarcinoma. The efficacy of PET maximum standardized uptake value (SUVmax) combined with HRCT signs in prediction of histopathologic subtype and growth pattern of lung adeno-carcinoma was evaluated. RESULTS. SUVmax was significantly higher in GGNs with invasive HRCT signs. The diameter of GGN (odds ratio, 1.660; p = 0.000) and the difference in attenuation value (odds ratio, 1.012; p = 0.011) between ground-glass components and adjacent lung tissues were independent predictors of FDG uptake by GGNs. SUVmax was higher in invasive adenocarcinoma than in adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA) (median SUVmax, 2.0 vs 1.1; p = 0.008). An SUVmax of 2.0 was the optimal cutoff value for differentiating invasive adenocarcinoma from AIS-MIA. Acinar-papillary adenocarcinoma had a higher SUVmax than lepidic adenocarcinoma (median SUVmax, 2.1 vs 1.3; p = 0.037). An SUVmax of 1.4 was the optimal cutoff value for differentiating the growth pattern of adenocarcinoma. Use of PET/CT with HRCT significantly improved efficacy for differentiating invasive adeno-carcinoma from AIS-MIA. However, use of HRCT cannot significantly improve the diagnostic efficacy of FDG PET in the evaluation of tumors with different growth patterns. CONCLUSION. FDG PET can be used to predict the histopathologic subtypes and growth patterns of early lung adenocarcinoma. Combined with HRCT, it has value for predicting invasive histopathologic subtypes but no significance for predicting invasive growth patterns.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common nonmelanoma skin cancer worldwilde, with a more invasive growth pattern and higher potential to metastatize than basal cell carcinoma. Although several risk factors have been linked to a high metastatic potential of cSCC, no widely accepted classification system for this common subtype of cancer exists. Herein we report an emblematic case of rapidly growing and metastatic cSCC and discuss the rate of growth of the tumour (ROG) as novel prognostic high risk surrogate marker.

1499 Purpose: Glioma is an invasive growth tumor that is difficult to resect completely. Accurate diagnosis of residual or recurrent disease post surgery is of great value for the selection of the postoperative treatments, evaluation of efficacy and prognosis. The purpose of this investigation was to assess the value of 11C-CHO and 18F-FDG PET/CT brain imaging in the differential diagnoses of contrast enhanced lesions shown on brain MRI. Methods: Thirty patients who had ring-shape enhanced intracerebral lesions on the MRI images in our hospital (17 males, 13 females, mean age: 61.23±8.00 years) underwent both 18F-FDG and 11C-CHO PET/ CT brain imaging. The results were analyzed in visually and semi-quantitatively. The final diagnoses were compared to surgical results and follow-up. Results: A total of 32 lesions were found on the 18F-FDG PET/CT images, We correctly diagnosed 14 cases of malignant lesions based on FDG PET/CT images. However, there were 5 cases of false negatives and 4 cases of false positives on 18F-FDG PET/CT brain scan. And the sensitivity, specificity and accuracy of 18F-FDG were 73.7%, 63.6% and 70.0%, respectively. In comparison, a total of 38 lesions showed on the 11C-CHO PET/CT images. We correctly identified 19 cases of malignant lesions based on 11C-CHO PET/CT images. There were 2 cases of false negatives and 1 case of false positive on 11C-CHO PET/CT scan.Meanwhile, the sensitivity, specificity and accuracy of 11C-CHO PET/CT brain imaging were 90.5%, 88.9% and 90.0%, respectively. Conclusions: Although both 18F-FDG and 11C-CHO PET/CT have value in the evaluation of ring-enhanced brain tumors shown on MRI, 11C-CHO PET/CT is more accurate. A combined use of the both tracers can improve the accuracy of the diagnosis of ring-enhanced lesions on brain MRI.

BACKGROUND We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns. METHODS Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3). RESULTS The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121). CONCLUSIONS This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.

Backgound. Pituitary adenomas (PA) are benign tumors, originated from the anterior pituitary tissue in the most cases. The notion of "invasiveness" is important in the planning phase of their treatment and capability for the prediction of the results. Objective. Invasiveness of pituitary adenomas, which includes the peculiar nature of the spread and extent of destructive tumor growth beyond the arachnoid capsule, still can not demonstrate unambiguous correlation with other morphological criteria and morpho-functional characteristics of the tumor. Methods. In this article the experience of diagnostics and treatment of 41 patients with pituitary adenomas with clinical manifestations of invasive growth is considered. Among them 29 (71%) women and 12 (29%) men aged from 19 to 75 years old. Prerequisite for inclusion in the study group was the intraoperative confirmation of tumor invasion. Results. In the most cases tumors grew through the wall of the cavernous sinuses, suprasellar spread or grew in sphenoid sinus. Spread of the tumor in the hypothalamic region and infrasellyar into the nasal cavity and sinus of the sphenoid bone were observed rarely. Indirect signs of tumor "activity" – a nuclear polymorphism, sites "fetal" structure were identified in 42% of cases. Increased mitotic and proliferative activities of the tumor were observed in 41.5% of cases. Conclusion. Morphological criteria of pituitary adenoma invasiveness require further improvement., Аденомы гипофиза (АГ) – в своем большинстве, доброкачественные опухоли, происходящие из ткани аденогипофиза. Важным на этапе планирования тактики их лечения и возможности прогнозирования результатов необходимо считать понятие „инвазивности”. Инвазивность аденом гипофиза, которая включает своеобразный характер распространения и степень деструктивного роста опухоли за пределы арахноидальной капсулы, до сих пор не находит однозначной корреляции с другими морфологическими критериями и морфо-функциональными характеристиками опухоли. В данной статье рассматривается опыт диагностики и лечения 41 пациента с аденомами гипофиза с клиническими проявлениями инвазивного характера роста, которые были прооперированы в клинике трансфеноидальной нейрохирургии внемозговых опухолей ГУ «Институт нейрохирургии НАМН Украины» в 2012-2014 годах. Опухоли в большинстве случаев прорастали стенки кавернозных синусов, распространялись супраселлярно или в клиновидную пазуху. Реже наблюдалось распространение опухоли в гипоталамическую область и инфраселлярно в полость носа и пазуху основной кости. В 42% наблюдений выявлялись косвенные признаки „активности” опухоли − ядерный полиморфизм, участки „фетального” строения. В 41,5% наблюдений установлено повышение митотической и пролиферативной активностей в опухоли. Индекс мечения Ki-67 в 60% случаев превышал 4%., Аденоми гіпофіза (АГ) – переважно доброякісні пухлини, що походять із залозистої тканини передньої частки гіпофізу. Інвазивність аденоми гіпофіза, яка включає своєрідний характер поширення та ступеня деструктивного росту пухлини за межі арахноїдальної капсули, не знаходить досі однозначної кореляції з іншими морфологічними критеріями та морфо-функціональними характеристиками пухлини. Проаналізовано результати діагностики і лікування 41 пацієнта з аденомами гіпофіза з клінічними ознаками інвазивного характеру росту, які були прооперовані в клініці трансфеноїдальної нейрохірургії позамозкових пухлин ДУ «Інститут нейрохірургії НАМН України» у 2012-2014 роках. Пухлини проростали стінки кавернозних синусів, розповсюджувались супраселлярно чи в клиноподібну пазуху, іноді – у ділянку гіпоталамуса чи інфраселлярно у порожнину носа та пазуху основної кістки – екстракраніально. В 42% спостережень виявлялись опосередковані ознаки „активності” пухлини − ядерний поліморфізм, ділянки „фетальної” будови, інвазію пухлини в оболонки головного мозку. В 41,5% спостережень встановлено підвищення мітотичної та проліферативної активності в пухлині. Індекс мічення Ki-67 в 60% випадків перевищує 4%.

The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic microsatellite unstable cancers. We observed that 25 (62.5 %) out of 40 assessable Lynch syndrome-associated carcinomas lacked evidence of polypous growth, compared to 17 (50 %) out of 34 sporadic MSI-H cancers. We detected CTNNB1 mutations in 8 (17.4 %) out of 46 Lynch syndrome-associated cancers compared to 0 out of 34 sporadic MSI-H cancers (p = 0.01). The majority of CTNNB1-mutant cancers presented with a histological appearance suggesting immediate invasive growth. Our results suggest that a distinct subgroup of CRCs in Lynch syndrome may in fact emerge from a non-polypous precursor, thus potentially explaining the phenomenon of interval cancers. Such a non-polypous precursor may be the recently described mismatch repair-deficient crypt focus, which remains invisible for the examiner during colonoscopy. This calls for considering the implementation of active, primary preventive measures in the management of Lynch syndrome. Future studies on pathogenic pathways and precursor lesions in Lynch syndrome are strongly encouraged, and the clinical efficacy of new prevention approaches should be evaluated in prospective clinical trials.

Aims The depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma (SCC). The threshold of 1 mm distinguishes between FIGO stages IA and >= IB disease and guides the need for groin surgery. Therefore, high interobserver agreement is crucial. The conventional and the alternative method are described to measure the depth of invasion. The aims of this study were to assess interobserver agreement for classifying the depth of invasion using both methods and to identify pitfalls. Methods and results Fifty slides of vulvar SCC with a depth of invasion approximately 1 mm were selected, digitally scanned and independently assessed by 10 pathologists working in a referral or oncology centre and four pathologists in training. The depth of invasion was measured using both the conventional and alternative method in each slide and categorised into 1 mm. The percentage of agreement and Light's kappa for multi-rater agreement were calculated, and 95% confidence intervals were calculated by bootstrapping (1000 runs). The agreement using the conventional method was moderate (kappa = 0.57, 95% confidence interval = 0.45-0.68). The percentage of agreement among the participating pathologists using the conventional method was 85.0% versus 89.4% using the alternative method. Six pitfalls were identified: disagreement concerning which invasive nest is deepest, recognition of invasive growth and where it starts, curved surface, carcinoma situated on the edge of the tissue block, ulceration and different measurement methods. Conclusions Pathologists reached only moderate agreement in determining the depth of invasion in vulvar SCC, without a notable difference between the two measurement methods.

International audience; Plant cells are enclosed in cell walls that weld them together, meaning that cells rarely change neighbours. Nonetheless, invasive growth events play critical roles in plant development and are often key hubs for the integration of environmental and/or developmental signalling. Here we review cellular processes involved in three such events: lateral root emergence, pollen tube growth through stigma and style tissues, and embryo expansion through the endosperm (Figures 1-3). We consider processes such as regulation of water fluxes and cell turgor (driving growth), cell wall modifications (e.g. cell separation) and cell death (for creating space) within these three contexts with the aim of identifying key mechanisms implicated in providing a chemical and biophysical environments permitting invasive growth events.

Condyloma acuminata, or anogenital warts, caused by human papillomavirus are the most common sexually transmitted disease. In rare cases, the disease could progress to an extensive neoplasm called Buschke–Löwenstein tumor (BLT), also known as giant condyloma acuminatum. BLT differs from normal condyloma acuminata by presenting with locally invasive growth, lack of spontaneous resolution, tendency for recurrence after treatment and potential for malignant transformation. We examine a BLT case reaching large dimensions in the anorectal region treated with neoadjuvant chemoradiation therapy and surgical excision of residual lesions. Furthermore, continuous follow-up care can help identify and prevent recurrence or malignant transformation of the tumor.

Gliomatosis cerebri (GC) is an aggressive glioma characterized by an invasive growth pattern and a dismal prognosis. The low incidence and non-specific symptoms at presentation pose unique challenges for early diagnosis and disease-specific research. There is no standard of care for the treatment of patients with a GC phenotype. Understanding the biology of this entity is a critical step in determining effective treatments. Toward this end, the Second International GC Group convened at National Institutes of Health, Bethesda on June 22nd–23rd 2017. This paper summarizes the main conclusions and recom-mendations for research priorities to fight this fatal condition.

Small HCCs, including seHCC and spHCC, are rarely encountered in daily practice. Definite diagnosis is difficult for general pathologists. In this study, we reviewed 1025 cases of HCC and examined the histologic characteristics of small HCCs to facilitate more accurate diagnosis. Slides of archived HCC cases were reviewed by 2 senior pathologists, and small HCCs were identified according to the canonical criteria. Additional immunohistochemical stains were performed. Thirty-seven cases of small HCC were identified, including 22 cases of seHCC and 15 cases of spHCC. We found 2 types of invasive growth patterns in these lesions. The first is the expansile invasive growth pattern, with monomorphic tumor cells penetrating through the incomplete fibrous capsules and expanding into the adjacent noncancerous liver with a spherical, hemispheric, or mushroom shape. The second is the classic stromal invasion pattern. At least one type of invasive pattern was observed in all of the 37 cases of small HCC, and the seHCCs exhibit the expansile invasive growth pattern more frequently than the classic stromal invasion pattern. On the contrary, stromal invasive pattern was more common in spHCC nodules. In conclusion, with the background of chronic hepatitis and cirrhosis, histologic features including crowdedness of hepatocytic trabeculae and the expansile invasive growth pattern are strong evidence for the diagnoses of small HCC.

The paper is devoted to the study of the expression of markers associated with invasive breast carcinoma. The study included a surgical material from 107 patients with invasive carcinoma of the non-specific type of breast cancer who had not previously received neoadjuvant therapy. The study revealed a number of markers related to invasive tumor growth, characterized by a pronounced heterogeneous expression pattern in all cases. Study of the expression of markers associated with invasive breast carcinoma showed that not all cells are able to promote invasive growth in different periods of time, but the fact of detecting the positive expression of the markers in tissue tumors indicates a more aggressive cancer phenotype with a high potential for invasion.

Pituitary adenomas without clinically active hypersecretion are summarized under the term nonfunctioning pituitary adenomas (NFPAs). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. Aim . To investigate the immunohistochemical and radiological features of NFPAs and assess the granins — chromogranin A (CgA), secretogranin II (SgII), secretoneurin (Sn) as immunohistochemical markers of NFPAs. Matherial and methods . 50 pituitary adenomas excised surgically were immunostained to reveal pituitary hormones, ki-67, CgА. SgII, Sn. All patients underwent MRI, invasive growth was estimated due to J.Hardy classification (1973). Results . 24 (51,1%) were gonadotropic tumors, 12 (25,5%) — null cell adenomas. Immunopositivity for ACTH was determined in 6 cases (12,7%), for GH in 5 (10,6%) cases, for PRL in 4 (8,5%). The median level of ki-67 was 2% (min. — 0.5%, max. — 7%). The CgA, SgII, Sn immunopositivity was found in 83, 93,6, 85,1% respectively, being more expressed in gonadotropinomas and null cell adenomas. Invasive growth was detected in 28 (44%) cases, among the invasive adenomas 22 tumors were giant. CgA expression is adverse prognostic factor, area under the curve (AUC) with 0,705. We did not find any correlation between ACTH-, STH-, CgII- and Sn- immunopositivity, ki-67 and invasive growth. Conclusions . Our work shows that a majority of NFPAs are truly secreting adenomas with significant numbers comprising potentially hazardous cortico- and somatotropinomas. CgA, SgII and Sn have a high expression in most of the NFPAs.

С целью иммуногистохимической оценки экспрессии маркеров прогрессирования в гепатоцеллюлярном и холангиоцеллюлярном раке печени разной величины с учётом площади иммунопозитивных клеток проведено патогистологическое и иммуногистохимическое исследование трепанобиоптатов печени 94 больных, среди которых 55 пациентов страдали гепатоцеллюлярной карциномой (ГЦК) и 39 – холангиоцеллюлярной карциномой (ХЦК) разной величины, измеренной при ультразвуковом исследовании печени. Фотоцифровой морфометрией определена площадь иммунопозитивных клеток, экспрессировавших Ki-67, р53, каспазу-3, Е-кадгерин, β-катенин, MMP-9 и ТІМР-1, в 21-й ГЦК и в 17-ти ХЦК диаметром до5 см, а также в 34 ГЦК и в 22 ХЦК диаметром более5 см. Установлено, что в ГЦК диаметром более5 см площадь клеток, экспрессировавших р53, Ki-67, β-катенин и ММР-9, статистически достоверно выше (в 2, 1,4, 1,8 и 1,6 раза соответственно), чем в ГЦК диаметром менее 5 см, а площадь Е-кадгерин-позитивных клеток в крупной опухоли в 1,8 раза меньше, чем в меньшей опухоли. В ХЦК диаметром более5 см площадь клеток, экспрессировавших р53, Ki-67, β-катенин и ММР-9, статистически достоверно выше (в 1,8 раза, 1,4 раза, 1,7 раза и 1,3 раза соответственно), чем в ХЦК диаметром менее 5 см, а площадь Е-кадгерин-позитивных клеток в крупной опухоли в 2 раза меньше, чем в малой опухоли. По данным сравнительного анализа, в ГЦК и ХЦК различного диаметра площади каспаза-3-позитивных и ТИМР-1-позитивных клеток статистически достоверно не отличаются. Таким образом, увеличение размеров ГЦК и ХЦК сопровождается гиперэкспрессией ядерного онкопротеина р53, повышением уровня пролиферации опухолевых клеток, утратой опухолевыми клетками межклеточных адгезивных связей и возрастанием экспрессии металлопротеиназы-9, что в совокупности способствует быстрому агрессивному и инвазивному росту этих опухолей в печени., Aim. Histopathological and immunohistochemical study of trephine biopsy of the liver in 94 patients, including 55 patients who suffered from hepatocellular carcinoma (HCC) and 39 - cholangiocellular carcinoma (CCC) with various sizes determined by ultrasound of the liver were carried out.Methods and results. The photo digital morphometry was used to estimate the area of immunopositive cells expressing Ki-67, p53, caspase-3, E-cadherin, β-catenin, MMP-9 and TІMR-1 in 21 HCC and 17 CCC up to5 cm in diameter and in 34 HCC and 22 CCC more than 5 cm in diameter. It is found that in HCC more than 5 cm diameter area of cells expressing p53, Ki-67, β-catenin and MMP-9 was significantly higher (2, 1.4, 1.8 and 1.6 times, respectively) than in the HCC with diameter less than 5 cm, and the area of E-cadherin-positive cells in the large tumors was 1.8 times less than in small ones. In the CCC with diameter greater than 5 cm area of cells expressing p53, Ki-67, β-catenin and MMP-9 was significantly higher (1.8, 1.4, 1.7 and 1.3 times, respectively) than in CCC with diameter less than 5 cm, and the area of the E-cadherin-positive cells in large tumor was two times less than in small tumors. According to the comparative analysis, in HCC and CCC of different diameters areas of caspase-3-positive and ТІМР-1-positive cells were not significantly different.Conclusion. Thus, increasing size of HCC and CCC is accompanied by the overexpression of nuclear oncoprotein p53, increased levels of tumor cell proliferation, tumor cell loss of intercellular adhesion bonds and an increase in the expression of metalloproteinase-9, all of which contribute to the rapid aggressive and invasive growth of tumors in the liver., З метою імуногістохімічного оцінювання експресії маркерів прогресування в гепатоцелюлярному та холангіоцелюлярному раку печінки різної величини з урахуванням площі імунопозитивних клітин виконали патогістологічне й імуногістохімічне дослідження трепанобіоптатів печінки 94 хворих, серед них 55 пацієнтів страждали на гепатоцелюлярну карциному (ГЦК) і 39 – на холангіоцелюлярну карциному різної величини, що визначена при ультразвуковому дослідженні печінки. Фотоцифровою морфометрією встановлена площа імунопозитивних клітин з експресією Ki-67, р53, каспази-3, Е-кадгерину, β-катеніну, MMP-9 і ТІМР-1, у 21-й ГЦК і в 17-ти ХЦК діаметром до 5 см, а також в 34-х ГЦК і у 22-х ХЦК діаметром більше ніж 5 см. Встановили, що у ГЦК діаметром більше ніж 5 см площа клітин з експресією р53, Ki-67, β-катеніну та ММР-9 статистично вірогідно вища (у 2, 1,4, 1,8 і 1,6 раза відповідно), ніж у ГЦК діаметром менше ніж 5 см, а площа Е-кадгерин-позитивних клітин у великій пухлині в 1,8 раза менша, ніж у малій. У ХЦК діаметром більше ніж 5 см площа клітин з експресією р53, Ki-67, β-катеніну і ММР-9, статистично достовірно вище (в 1,8 раза, 1,4 раза, 1,7 раза та 1,3 раза відповідно), ніж в ХЦК діаметром менше ніж 5 см, а площа Е-кадгерин-позитивних клітин у великій пухлині вдвічі менша, ніж у малій пухлині. За даними порівняльного аналізу, у ГЦК і ХЦК різного діаметра площі каспаза-3-позитивных і ТІМР-1-позитивних клітин статистично вірогідно не відрізняються. Отже, збільшення розмірів ГЦК і ХЦК супроводжується гіперекспресією ядерного онкопротеїну р53, підвищенням рівня проліферації пухлинних клітин, втратою пухлинними клітинами міжклітинних адгезивних зв'язків і зростанням експресії металопротеїнази-9, що в сукупності сприяє швидкому агресивному й інвазивному росту цих пухлин у печінці.