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Objectives: To analyze the published evidence for the use of fallopian tube brush cytology for the early detection of extrauterine serous gynecological cancer. Methods: We systematically searched the literature and, additionally, cross checked on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of fallopian tube brush cytology and its applications in the diagnosis, screening or follow up of extrauterine serous gynecological cancer. Results: The search strategy resulted in 21 abstracts or full-text articles, 5 of which met the inclusion criteria. The year of publication ranged from 2016 to 2022, and a total of 193 fallopian tube samples were investigated. Cytobrush, Tubebrush©, and Cytuity™ were used to obtain salpingeal samples for liquid-based cytology evaluation. Conclusions: Our findings indicate that, at present, there is a lack of satisfying evidence-based data in the literature which would support the implementation of fallopian tube brush cytology as an adjunctive tool for early detection of extrauterine serous gynecological cancer. Thus, we believe that there is need for well-designed clinical studies to assess the effectiveness and diagnostic accuracy of the method as well as to validate the cytological criteria for the diagnosis and prediction of gynecological malignancies.

Extramedullary relapse of leukemia is encountered more often than in the past. The reason is that leukemia survival rates increase with improved treatment schemes. We present a rare case of involvement of the cervix of the uterus in an adult B Acute Lymphocytic Leukemia (B-ALL) survivor. Relapses affect various organs but rarely the female genital tract. Nevertheless, in this case, a woman with a history of induced amenorrhea due to treatment for leukemia presented to the gynecologist because of vaginal spotting. Colposcopy evaluation of the vagina/cervix, sonography and cytological and histological sampling established the diagnosis of leukemia relapse in the cervix of the uterus. Under these circumstances, our study highlights the rare extramedullary presentation of leukemia in the cervix of the uterus of a young lady considered to be disease-free and listed for bone marrow transplantation. In this rare case of relapse in the cervix of the uterus, Pap smears alarmed physicians, and radiology examinations assisted the diagnostic workup. Still, only biopsy, microscopic evaluation, and immunohistochemistry studies established the exact diagnosis. Prognosis in the situation of extramedullary disease relapse in the female genital tract was poor, but gynecologists’ high suspicion led to a prompt diagnosis. Survival is in general limited, but together with high suspicion, multidisciplinary team involvement is imperative to improve the reduced chances of survival.

Histone H2AX undergoes phosphorylation as an answer to DNA double-strand breaks, which in turn are part of the oncogenic procedure. The detection of gamma-H2AX can potentially serve as a biomarker for transformation of normal tissue to premalignant and consequently to malignant tissues. The aim of this study was to evaluate the clinical significance of gamma-H2AX expression in breast cancer. Gamma-H2AX expression in tissues from 110 breast cancer patients was analyzed by immunohistochemistry and correlated with clinicopathological variables. Greater tumor size, higher grade, and the number of affected lymph nodes are significantly associated with greater values of gamma-H2AX. In addition, gamma-H2AX differs significantly among patients’ International Federation of Gynecology and Obstetrics stage. Higher values of estrogen receptor and progesterone receptor are significantly associated with lower gamma-H2AX values. In conclusion, a positive association between gamma-H2AX expression and infaust histopathological parameters was observed.

Malignant myoepithelioma of the breast is an extremely rare tumor composed entirely or almost entirely of malignant spindle cells with myoepithelial differentiation. Only a limited number of case reports have been descibed to date; therefore the biological behavior and treatment outcomes of this rare tumor have not been clearly determined. Herein, we present a case of a 74-year-old woman who was admitted with inflammatory-like cancer of the breast, presenting with invasion of the chest wall and axillary lymph node metastasis at the time of diagnosis. The histological examination revealed a tumor composed of epithelioid and spindle cells with moderate to marked nuclear atypia, with foci of hemorrhage and necrosis. The tumor cells were immunoreactive for vimentin, p63, p53, CD10, cytokeratin (CK)8/18, CKAE1-3 and S-100. Finally, a diagnosis of myoepithelial carcinoma of the breast was established. Neoadjuvant chemotherapy was first administered and proved to be ineffective. Due to locoregional progression that was associated with the development of an abscess and subsequent excessive bleeding, a palliative mastectomy was performed. Postoperatively, one more cycle of systemic chemotherapy was administered. However, the patient experienced an early relapse to the chest wall and succumbed to septic shock due to persistent local infection. The aggressiveness and chemoresistance of the tumor in this case was consistent with the existing bibliography.

Background-Aim: The aim of the present study was to explore the efficacy of dose-dense sequential adjuvant chemotherapy followed by trastuzumab in HER2-positive patients according to the immunohistochemically (IHC) defined subtypes. Patients and methods: A total of 771 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples, prospectively collected from 990 eligible patients with high-risk N0 or N1 operable breast cancer participating in a phase III trial (HE10/05), were centrally assessed in tissue microarrays by IHC for 6 biological markers, that is, estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, cytokeratin 5 (CK5) and EGFR. All cases were further evaluated for HER2 amplification by FISH. Patients were classified as: luminal A (ER/PgR-positive, HER2-negative, Ki67low, N=382, 49.5%); luminal B (ER/PgR-positive, HER2-negative, Ki67high, N=136, 17.6%); luminal-HER2 (ER/PgR-positive, HER2-positive, N=125, 16.2%); HER2-enriched (ER-negative, PgR-negative, HER2-positive, N=63, 8.2%); triple-negative (TNBC) (ER-negative, PgR-negative, HER2-negative, N=65, 8.4%); and basal core phenotype (BCP) (TNBC, CK5-positive and/or EGFR-positive, N=53, 6.9%). Results: At a median follow-up of 60.5 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates for the total patient population were 88.3% and 96.0%, respectively. The 3-year DFS rates for luminal A, luminal B, luminal-HER2, HER2-enriched, TNBC and BCP patients were 91.1%, 88.2%, 86.4%, 93.7%, 87.7%, and 89.4%, respectively, while the corresponding 3-year OS rates were 95.8%, 95.6%, 97.6%, 95.2%, 95.4%, and 95.0%, respectively. No significant differences were detected for either 3-year DFS or OS in the immunohistochemically defined subtypes, except a trend for significantly worse DFS in patients with luminal-HER2 tumors compared to patients with HER2-enriched tumors (log-rank, p=0.069). Conclusions: In the post-trastuzumab era, at a relatively short follow-up, the luminal-HER2 patients show a trend for worse DFS compared to patients with HER2-enriched tumors treated with dose-dense sequential adjuvant chemotherapy followed by trastuzumab. No other significant differences were detected, with follow-up however being continued. Citation Format: George Fountzilas, Eleni Timotheadou, Georgia Gourgioti, Petroula Arapantoni-Dadioti, Sotiris Lakis, Anna Batistatou, Triantafyllia Koletsa, Olympia Tzaida, Mattheos Bobos, Alexandra Papoudou-Bai, Eleftheria Tsolaki, Sofia Chrisafi, Elena Fountzilas, Ioannis Efstratiou, Helen Gogas, Flora Zagouri, Dimitrios Pectasides. Prognostic value of immunophenotypically defined subtypes in patients treated with dose-dense sequential adjuvant chemotherapy in the trastuzumab era. A Hellenic Cooperative Oncology Group study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-07.

Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. Carcinomas of accessory breast tissue account for ∼0.3% of breast cancers, 5% of which are arising within a supernumerary breast. They are usually diagnosed at a later stage compared with breast cancer, due to their rarity and low clinical suspicion.We present the case of a 58 years old male who was admitted to our hospital for an umbilical hernia, surgical repair. During surgery a small skin biopsy was excised and sent for pathological examination as routine procedure. The histological report revealed the presence of a poorly differentiated carcinoma. Immunochemical analysis confirmed adenocarcinoma of breast origin.Carcinomas of accessory breast tissue are rare and therefore they are usually of advanced stage in time of diagnosis. Few cases have been reported in literature of accessory breast tissue carcinomas in men. To the best of our knowledge, this is the only case in the literature, of ectopic breast tissue cancer in the umbilicus.Ectopic breast, Male breast cancer, Umbilicus.La sede ectopica di tessuto ghiandolare mammario è un’eventualità rara, con un’incidenza del 1-2% nella popolazione generale. I carcinomi insorti in questi tessuto mammari accessori rappresentano circa il 0,3% di tutti i cancri della mammella, 5% dei quali insorti su mammelle soprannumerarie. La loro diagnosi avviene in fase più avanzate che nel caso dei correnti cancri della mammelle in relazione alla loro rarità ed al basso livello di sospetto clinico. Qui è presentato il caso di un uomo di 58 anni ricoverato nel nostro ospedale per la riparazione chirurgica di un’ernia ombelicale. Durante l’intervento venne eseguita una piccola biopsia cutanea per esame istologico quale procedura usuale. Il referto istologico ha rivelato la presenza di un carcinoma scarsamente differenziato, che all’analisi immunoistochimica si è dimostrato essere un adenocarcinoma di origine mammaria. Si conferma la rarità dei carcinomi insorti su tessuto ghiandolare mammario accessorio, che sono per lo più in fase avanzata al momento della diagnosi. Pochi di questi casi sono riportati in letteratura in relazione a tessuto mammario accessorio nel sesso maschile, ed a nostra conoscenza questo è l’unico in letteratura di tessuto mammario carcinomatoso a sede ectopica nell’ombelico.

Σκοπός: Διερεύνηση προγνωστικής αξίας ογκοπρωτεϊνών οικογένειας HER:HER1/ΕGFR και HER2 σε ασθενείς με καρκίνωμα μαστού υψηλού κινδύνου που αντιμετωπίσθηκαν με επικουρική, εντατικοποιημένη, διαδοχικά χορηγούμενη χημειοθεραπεία. Συσχέτιση των δεικτών με κλινικές και ιστοπαθολογικές παραμέτρους και με την p53 πρωτεΐνη. Διερεύνηση προβλεπτικής αξίας τους σε σχέση με ταξάνη: πακλιταξέλη (Taxol). Ασθενείς -μέθοδος: 595 ασθενείς με ιστολογικά διαγνωσμένο καρκίνωμα μαστού υψηλού κινδύνου, τυχαιοποιήθηκαν σε 2 ομάδες ΧΜΘ. Σχήμα (Α) 3 κύκλων: επιρουβικίνης (Ε) (110mg /m2) - πακλιταξέλης (Τ) (250mg/m2) -εντατικοποιημένου CMF (κυκλοφωσφαμίδη 840mg/m2, μεθοτρεξάτη 47mg/m2, φλουουρακίλη 840mg /m2). Σχήμα (Β) 4 κύκλων: επιρουβικίνης (Ε) - CMF ιδίων δόσεων και μεσοδιαστημάτων (δύο εβδομάδων). Ανοσοϊστοχημική (IHC) αναζήτηση HER1 και p53 πρωτεΐνης σε 312 και 307 ασθενείς αντίστοιχα. Μελέτη HER2 κατάστασης IHC σε 308 ασθενείς και με φθορίζοντα in situ υβριδισμό (FISH) στις περιπτώσεις που χαρακτηρίσθηκαν IHC ως 2+. Αποτελέσματα:Ανάδειξη HER1 έκφρασης σε 17% και HER2 υπερέκφρασης σε 30,5% των ασθενών. Η HER1 έκφραση συσχετίσθηκε σημαντικά με αρνητικούς ορμονικούς υποδοχείς ΕR/PR (50% vs 18%, p5 cm: 18% vs 16%, p=0.04), HER1 έκφραση (25.5% vs 13%, p=0.01) και p53 έκφραση (40% vs 17%, p

The uterus is an extremely rare location for a primary or metastatic melanoma. We describe the ultrasonographic appearance of a malignant melanoma of the uterus presenting clinically as a large mass in a 78-year-old woman. Transabdominal sonography revealed a solid uterine mass measuring 13 × 11.5 × 8.5 cm with inhomogeneous echotexture and bright internal echoes. The tumor showed a diffuse spread inside the uterine corpus, and the endometrium was not demonstrated ultrasonographically. © 2005 Wiley Periodicals, Inc. J Clin Ultrasound33:424–427, 2005

Background HER2 and TOP2A parameters (gene status, mRNA and protein expression) have individually been associated with the outcome of patients treated with anthracyclines. The aim of this study was to comprehensively evaluate the prognostic/predictive significance of the above parameters in early, high-risk breast cancer patients treated with epirubicin-based, dose-dense sequential adjuvant chemotherapy. Methods In a series of 352 breast carcinoma tissues from patients that had been post-operatively treated with epirubicin-CMF with or without paclitaxel, we assessed HER2 and TOP2A gene status (chromogenic in situ hybridization), mRNA expression (quantitative reverse transcription PCR), as well as HER2 and TopoIIa protein expression (immunohistochemistry). Results HER2 and TOP2A amplification did not share the same effects on their downstream molecules, with consistent patterns observed in HER2 mRNA and protein expression according to HER2 amplification (all parameters strongly inter-related, p values < 0.001), but inconsistent patterns in the case of TOP2A. TOP2A gene amplification (7% of all cases) was not related to TOP2A mRNA and TopoIIa protein expression, while TOP2A mRNA and TopoIIa protein were strongly related to each other (p < 0.001). Hence, TOP2A amplified tumors did not correspond to tumors with high TOP2A mRNA or TopoIIa protein expression, while the latter were characterized by high Ki67 scores (p = 0.003 and p < 0.001, respectively). Multivariate analysis adjusted for nodal involvement, hormone receptor status, Ki67 score and HER2/TOP2A parameters revealed HER2/TOP2A co-amplification (21.2% of HER2 amplified tumors) as an independent favorable prognostic factor for DFS (HR = 0.13, 95% CI: 0.02-0.96, p = 0.046); in contrast, increased HER2/TOP2A mRNA co-expression was identified as an independent adverse prognostic factor for both DFS (HR = 2.41, 95% CI: 1.31-4.42, p = 0.005) and OS (HR = 2.83, 95% CI: 1.42-5.63, p = 0.003), while high TOP2A mRNA expression was an independent adverse prognostic factor for OS (HR = 2.06, 95% CI: 1.23-3.46, p = 0.006). None of the parameters tested was associated with response to paclitaxel. Conclusions This study confirms the favorable prognostic value of HER2/TOP2A co-amplification and the adverse prognostic value of high TOP2A mRNA expression extending it to the adjuvant treatment setting in early high-risk breast cancer. The strong adverse prognostic impact of high HER2/TOP2A mRNA co-expression needs further validation in studies designed to evaluate markers predictive for anthracyclines. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12611000506998.

We aimed to determine whether a standard P504S, 34betaE12 and p63 immunostaining of prostate core needle biopsy specimens can optimize diagnostic accuracy of conventional staining methods.The staining properties of all three antibodies were evaluated on 250 prostate biopsies formerly diagnosed as benign.Lack of basal cell staining in more than three glands for 34betaE12 and p63 occurred in 41 (27.5%) and 9 (6%) respective cases from the General Hospital pool. Respective figures from the Uropathology department specimens were 18 (18%) for 34betaE12 and 8 (8%) for p63. With the aid of P504S positivity, a case of prostate cancer as well as another of atypical small acinar proliferation was discovered.Despite its potential for important aid in accurate diagnosis, standard application of immunohistochemistry in prostate biopsy is not justified and should be reserved for equivocal cases where conventional pathology fails to be conclusive.

Background: To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy. Methods: 595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients. Results: HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07). Conclusion: The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.

PURPOSE: To assess the prognostic and predictive significance of p53 and Bcl-2 protein expression in high risk patients with breast cancer treated with dose-dense sequential chemotherapy. PATIENTS AND METHODS: From June 1997 until November 2000, 595 patients were randomized to three cycles of epirubicin (E) 110 mg/m2 followed by three cycles of paclitaxel (P) 250 mg/m2 followed by three cycles of 'intensified' CMF (cyclophosphamide 840 mg/m2, methotrexate 47 mg/m2 and fluorouracil 840 mg/m2) or to four cycles of E, followed by four cycles of CMF. p53 and Bcl-2 expression was investigated by immunohistochemistry in 392 and 397 patients respectively. RESULTS: Positive expression of p53 was detected in 104 (26.5%) patients and was significantly associated with negative hormonal status, worse histologic grade, higher incidence of disease relapse and higher rate of death. p53 positive expression was a significant negative predictor of overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.001). Negative expression of Bcl-2 was detected in 203 (51%) patients and was significantly associated with negative hormonal status. Multivariate analysis revealed that, positive p53 expression, higher number of positive nodes and worse tumor grade were related to significantly poorer OS and DFS. CONCLUSIONS: For both treatments, p53 positive expression was a significant negative prognostic factor for OS and DFS while Bcl-2 was not. No predictive ability of p53 status or Bcl-2 status for paclitaxel treatment was evident. Ann Oncol

e21059 Background: The prognostic/predictive value of HER2 and topoisomerase II alpha (TOP2A) gene status in patients with breast cancer treated with adjuvant dose-dense sequential chemotherapy is ...