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Salivary gland hypofunction adversely affects the oral environment and daily life by causing dry mouth (xerostomia). Senescence-related atrophy of salivary gland tissues is one cause of xerostomia, and it is particularly common among the elderly. However, the underlying mechanism is poorly understood, and no treatment has been established. Therefore, we examined age-related changes in senescence-associated secretory phenotype (SASP) factors, which regulate stemness and cellular senescence, in mouse submandibular glands. We analyzed the submandibular glands of 6-week-old (young group, n = 6) and 82-week-old mice (aged group, n = 6). We performed salivary flow rate measurements, histological analysis including immunohistochemistry, and quantitative real-time PCR. The salivary flow rate was significantly lower in the aged group than in the young group. In addition, immunostaining and quantitative real-time PCR illustrated that aquaporin-5 and α-amylase expressions were significantly decreased in aged mice, indicating salivary gland hypofunction. c-Kit and cytokeratin 5 expressions were also significantly decreased in this group, suggesting that the regenerative abilities of the submandibular glands were reduced because of decreased stem and progenitor cell counts. Furthermore, the levels of p16INK4a and p21 (the senescence markers) and TGF-β1 and IL-6 (SASP factors) were significantly increased in mice, suggesting that senescence had been promoted. The decreased numbers of stem and progenitor cells and increased levels of SASP factors might be associated with age-related changes in mouse submandibular glands. These results might facilitate the development of treatments for senescence-related submandibular gland hypofunction. [ABSTRACT FROM AUTHOR]

Objective: Traditionally, the diagnosis of pleural mesothelioma is based on histological material. Minimally invasive effusion cytology specimens are an alternative that, like biopsies, require ancillary analyses. Validation of immunohistochemical (IHC) analyses on cytology, including the surrogate markers for molecular alterations BAP1 and MTAP, is of interest. Methods: IHC for eight different markers was performed on 59 paired formalin‐fixed, paraffin‐embedded pleural biopsies and pleural effusion cell blocks with mesothelioma. Immunoreactivity in ≥10% of tumour cells was considered positive/preserved. The concordance between histological and cytological materials was assessed. Results: The overall percentage of agreement between the histological epithelioid component in 58 biopsies and paired cell blocks was 93% for calretinin, 98% for CK5, 97% for podoplanin, 90% for WT1, 86% for EMA, 100% for desmin, 91% for BAP1, and 72% for MTAP. For 11 cases with biphasic or sarcomatoid histology, the concordance between cytology and the histological sarcomatoid component was low for calretinin, CK5, and WT1 (all ≤45%). For the whole cohort, loss of both BAP1 and MTAP was seen in 40% while both markers were preserved in 11% of the biopsies for epithelioid histology. The corresponding numbers were 54% and 8%, respectively, for the paired cell blocks. Conclusions: Generally, a high concordance for IHC staining was seen between paired biopsies and pleural effusion cell blocks from mesotheliomas, but the somewhat lower agreement for WT1, EMA, and especially MTAP calls for further investigation and local quality assurance. The lower concordance for the sarcomatoid subtype for some markers may indicate biological differences. [ABSTRACT FROM AUTHOR]

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels. [ABSTRACT FROM AUTHOR]

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. [ABSTRACT FROM AUTHOR]

Objective To investigate the expression of CK5 and CK20 in upper urinary tract urothelial carcinoma (UTUC) so as to explore the predictive value of CK5 and CK20 for the disease. Methods The clinical data of 101 UTUC patients admitted to our department from December 2012 to December 2018 were collected and retrospectively analyzed. The expression of CK5 and CK20 in tumor tissues was detected by immunohistochemical assay. The associations of CK5 and CK20 expression with the pathological features of tumor were analyzed. Kaplan-Meier survival curve was used to investigate the postoperative survival of the patients, and COX proportional risk regression model was adopted to analyze the relationships of CK5 and CK20 with the prognosis of these patients. Results According to the immunohistochemical results, the 101 patients were classified into 4 subtypes: CD5+CD20- (n=30, 29.7%), CD5+CD20+ (n=32, 31.7%), CD5-CD20- (n=26, 25.7%), and CD5-CD20+ (n=13, 12.9%). Kaplan-Meier univariate analysis and survival curve indicated that the overall survival (OS) (P < 0.001) and cancer-specific survival (CSS) (P < 0.001) of the patients were significantly worst in the CD5-CD20+ group than the other 3 groups. COX univariate and multivariate regression analyses showed that tumor grade, T stage, lymph node metastasis, and CD5-CD20+ subtype (for OS: HR=5.663, 95%CI: 1.392~23.050, P=0.015; for CSS, HR=7.962, 95%CI: 1.763~35.955, P=0.007) were independent risk factors for the prognosis of UTUC patients. Conclusion Combined detection of CK5 and CK20 expression can predict the prognosis of patients with UTUC, and those presenting CD5-CD20+ subtype have poorer prognosis, higher tumor stage and more prone to lymph node metastasis.

Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS.

Background: Sinonasal inverted papilloma (SNIP) is a benign epithelial tumor with distinctive histopathological features. However, the role of inflammation in SNIP remains poorly characterized., Objectives: This study aimed to compare the histopathological patterns and inflammatory characteristics of SNIP with those of chronic rhinosinusitis with nasal polyps (CRSwNPs) or normal ethmoid sinus mucosa., Methods: Fifty-eight tissue biopsies were prospectively collected from 38 patients with SNIPs, 12 CRSwNPs, and 8 normal ethmoid sinus mucosae. SNIP was histopathologically divided into four grades based on the extent of epithelial remodeling. The immunohistochemical characteristics of epithelial remodeling (p63, CK5) and infiltration of inflammatory cells (eg, eosinophils, neutrophils, and macrophages) and cytokines (eg, interleukin-1β, interleukin-6, and tumor necrosis factor-α) were analyzed., Results: Among the 38 SNIPs, 21.1%, 36.8%, 23.7%, and 18.4% were grades I, II, III, and IV, respectively. The expression levels of p63 and CK5 were significantly higher in SNIP than in the other two groups (both, p  < 0.05). Neutrophil and macrophage infiltration was more pronounced in SNIP and with differences among the four grades. The expression levels of inflammatory cytokines were significantly higher in the SNIP group than in the CRSwNP group. A positive correlation between the expression levels of p63 and inflammatory cytokines was observed in both SNIPs and CRSwNPs., Conclusion: Excessive epithelial remodeling is an important histological feature of SNIP; it is accompanied by sinonasal mucosal inflammation., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cytokeratin 5 is a marker of basal molecular subtypes of muscle‐invasive bladder cancer (MIBC), which correlates with worse overall survival compared to luminal subtypes. Our observations have not confirmed CK5 as a marker of high‐grade (HG) disease in Ta non‐muscle‐invasive bladder cancer (NMIBC). Therefore, to understand the basal‐luminal immunohistochemistry profile in Ta NMIBC, we performed immunohistochemistry for CK5, P40, P63 (basal), GATA3 and CK20 (luminal) and studied the correlation with HG and clinical outcome in 109 patients with Ta NMIBC. HG and low‐grade (LG) diseases were scored in each patient. Four different CK5 patterns were evaluated: absent (median 41.3%), normal (72.5%), rising (84.4%) and full thickness (23.9%). The median percentage of GATA3 was 100%. HG disease and CK5 expression and rising CK5 pattern had a significant inverse correlation, whereas HG disease and CK20 expression had a significant positive correlation. We also found a significant inverse correlation between CK5 expression and CK20 expression. Quantitative PCR confirmed that the presence of CK5 correlated with up‐regulation of CK5 RNA. None of the markers could differentiate patients with regard to clinical outcome. Our results suggest a role for CK5 and CK20 in differentiating between LG and HG disease in Ta NMIBC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fibrous pseudotumor is a rare benign lesion, reactive in nature, which can appear in the form of nodules (single or multiple) or diffusely in the testicular tunics. Clinically it simulates a malignant tumor, so the treatment consists of radical orchiectomy. CLINICAL CASE: A 70-year-old man, who came to the clinic due to an increase in testicular volume of several months of evolution. Ultrasound revealed a right simple hydrocele, 170 cm3. Treatment consisted of hydrolectomy, using the right hemiscrotal technique. In the surgical act, multiple nodules adhered to the tunica vaginalis and albuginea were evidenced. Immunohistochemistry showed positivity for caldesmon and CK (AE1 / AE3), and negativity for desmin, actin, CD34, CD31, calretinin, EMA, CK7, CK5 / 6 and WT1. The final diagnosis was: multiple nodular fibrous pseudotumor. CONCLSUIONS: It is important to know the fibrous pseudotumor, since when obtaining an intraoperative biopsy it can be confused with a high-grade lesion. The possibility of IgG4 disease should be ruled out, because it is a systemic disease that can affect any location. [ABSTRACT FROM AUTHOR]

Background: The potentially curative and/or palliative therapy for non‐resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub‐typing of non‐small cell lung carcinoma (NCSLC) has become paramount. Objectives: As there are few data from South Africa, we aimed to determine utility of TTF‐1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin‐fixed paraffin‐embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas. Methods: All cases of NSCLC diagnosed during a 3‐year period were retrospectively identified. All FNA biopsy and formalin‐fixed paraffin‐embedded cases that were stained with TTF‐1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data. Results: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF‐1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF‐1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma. Conclusion: All four immunostaining methods had high sensitivities. TTF‐1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF‐1. The specificity of CK5 for squamous cell carcinoma was higher than p63. Utility of TTF‐1, NapsinA, Ck5 and p63 in distinguishing between Adenocacinoma and Squamous cell carcinoma, using fine needle aspiration cellblock material and paraffin embedded biopsy specimens in a resource limited setting. [ABSTRACT FROM AUTHOR]

Therapeutic irradiation for cancers of the head and neck causes serious and irreversible damage to the salivary glands; the resulting adverse effects on salivary quality and quantity produce detrimental effects on teeth and oral mucosa. The salivary effects have been related mostly to loss of serous acini; damage to the ducts is relatively minor. Other radiation effects include fibrosis, adiposis and vascular damage. Stem cells in the salivary gland ducts have the potential to generate acinar cells in vitro and in vivo. I investigated the ducts and vasculature in irradiated and normal human submandibular glands using immunohistochemical localization of biomarkers of stem cells, duct function and blood vessels. Stem cell markers CK5 and Sca-1 labeled the cytoplasm of the basal and intercalated duct cells and all duct cells, respectively, in both normal and irradiated glands. CA IV, which participates in regulating salivary electrolytes and acid-base balance, labeled the cytoplasm of all ducts. CD34 labeling demonstrated more extensive vasculature in the irradiated glands than in the normal glands. My findings suggest that duct stem cells and at least one duct function persisted, and the vasculature was greater, despite moderate fibrosis, in the irradiated gland.

Objectives: Breast tumor resembling tall cell variant of papillary thyroid carcinoma (BTRPTC) is a rare breast lesion that is unrelated to thyroid carcinoma. Morphologically, it shows a solid papillary lesion with bland cytology, eosinophilic/amphophilic secretions, nuclear grooves, reversal of nuclear polarity (recently described), and nuclear inclusions. Clinical course is often uneventful with few exceptions reported in the literature. Herein, we report three additional cases.Methods: Immunohistochemical staining and next-generation sequencing was performed on all three cases.Results: The lesional cells on all cases were positive for cytokeratin 5 and S100, with weak expression/lack of estrogen receptor. No staining was observed for myoepithelial markers (p63 and myosin heavy chain) around the lesion. IDH2 mutations were identified in two cases at nucleotide 172 (cases 1 and 3). ATM gene mutation was identified in cases 2 and 3 and PIK3CA mutation in case 3. All patients are currently without disease.Conclusions: BTRPTC is a slow-growing neoplastic lesion that needs to be distinguished from other papillary lesions for optimizing therapy. [ABSTRACT FROM AUTHOR]

We investigated the entire length of the main excretory ducts (MED) of the major sublingual, parotid and submandibular salivary glands of mature laboratory rats for mucous (goblet) and luminal ciliated cells, biomarkers of cell proliferation, apoptosis, and five biomarkers of stem cells. Spleen and testis were used as positive controls. We used formalin fixed, paraffin embedded tissues. No mucous cells or cells with luminal cilia were observed in hematoxylin and eosin, alcian blue or periodic acid-Schiff stained sections. Immunohistochemistry using rabbit anti-rat antibodies produced anomalous reactions with cleaved caspase-3 for apoptosis, Ki-67 for proliferative activity and Sox 2. Following antigen retrieval, no primary antibody and all three negative controls, labeled macrophages appeared in the spleen. TUNEL staining revealed a few cells per section undergoing apoptosis. Reactions deemed valid occurred in MED with cytokeratin-5 and c-Kit and stem cell antigen 1 (Sca-1) mostly in the gland and middle segments. Other ducts, but not acini or myoepithelial cells, also were variably stained with c-Kit and Sca-1.

Relevant protein expression of GATA6, CK5, vimentin, and mucins using immunohistochemistry was assessed for predicting the prognosis of and chemotherapy efficacy in patients with pancreatic cancers (PCs). The protein expression was examined in 159 PCs resected after neoadjuvant chemotherapy (NAC-PCs) and compared with that of 120 matched biopsy specimens taken before NAC. KRAS mutations were assessed by digital PCR. NAC-PCs were classified by GATA6 expression initially and CK5 expression subsequently into 4 types: classical-type (n = 22) with GATA6-high (≥50%)/CK5-low (<10%) PCs; hybrid-type (n = 45) with GATA6-high/CK5-high (≥10%) PCs; basal-like-type (n = 53) with GATA6-low (<50%)/CK5-high (≥30%) PCs; and null-type (n = 39) with GATA6-low/CK5-low (<30%) PCs, which resulted in clear stratification of patient prognosis. The classical-type was associated with the most favorable prognosis, whereas the null-type was associated with the worst prognosis (multivariate hazard ratio: 3.56; 95% CI, 1.63-7.77; P = .0015). The hybrid and basal-like types correlated with in-between levels of prognosis. The risk of hepatic recurrence was lower in the classical-type than in null (multivariate odds ratio [mOR]: 0.18; 95% CI, 0.04-0.96; P = .0449) and basal-like (mOR: 0.24; 95% CI, 0.05-1.16; P =.0750) types. By contrast, the risk of locoregional recurrence was higher in the classical-type than in the basal-like-type (mOR: 5.03; 95% CI, 1.20-21.1; P = .0272). The hybrid-type was subclassified into transition and coexpression patterns with different gastric mucin expression levels. High levels of vimentin (≥10%, n = 30) in pre-NAC-PC tissues was associated with poor prognosis (P = .0256). Phenotypic transitions between pre-NAC and post-NAC-PCs were common (73/120; 61%). PCs with NAC regression grades 2 and 3 showed a transition to poorer prognostic phenotypes (P = .0497). KRAS mutations were not associated with these phenotypes. In conclusion, GATA6 and CK5 immunohistochemical expression phenotypes may stratify the survival of patients with NAC-PCs and reflect post-NAC phenotypic transitions associated with poor prognosis. Prompt evaluation of immunohistochemical phenotypes may contribute to designing a precision therapeutic strategy for patients with PCs., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels., (© 2023. The Author(s).)

Objectives: To assess immunohistochemical (IHC) stains differentially expressed between different types of lung cancer.Methods: We evaluated 16 different IHC stains in 209 prospectively included, surgically treated primary lung cancers, including 121 adenocarcinomas, 65 squamous cell carcinomas, 15 large-cell carcinomas, 5 adenosquamous carcinomas, 2 sarcomatoid carcinomas, and 1 small-cell carcinoma, using the tissue microarray technique.Results: Cytokeratin 5 (CK5) and P63 were both positive in 10% or more of the cells in 97% of the squamous cell carcinomas, with the former being positive (<10% of the cells) in only 2 non-squamous cell carcinomas. Thyroid transcription factor 1 (TTF1) and napsin A were positive in 10% or more of the cells in 88% and 87% of the adenocarcinomas, respectively, with 94% of the adenocarcinomas being positive in at least 1 marker. Fifteen percent of the adenocarcinomas were positive for estrogen receptor.Conclusions: CK5, TTF1, and napsin A are sensitive markers for squamous cell carcinoma and adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

We aimed to delineate the morphogenesis of aberrant nuclear features of urothelial carcinoma ( UC) cells in association with cytokeratin ( CK) expression patterns and cell proliferation activity. Correlation analysis of the nuclear area by morphometry and the expression patterns of CK5, CK20 and Ki-67 by triple immunofluorescence analysis was applied to 1699 cells from five low-grade and seven high-grade cases of UC. The majority of UC cells showed aberrant cellular differentiation represented by abnormal CK expression patterns of CK5(+)/ CK20(+) (40.5%) or CK5(−)/ CK20(+) (56.0%). CK5(+)/ CK20(−) cells, a phenotype of cancer stem/progenitor cells, represented a very small population (1.9%) and showed a low proliferation activity. Ki-67(+) cells showed a significantly different CK expression pattern compared with that of Ki-67(−) cells. The nuclear areas of CK5(−)/ CK20(+) cells (71.3 ± 25.9 μm2) were significantly larger than those of CK5(+)/ CK20(+) cells (66.6 ± 25.5 μm2). Negativity for CK5 was related to the grade of UC and an increased number of CK5(−)/ CK20(+)/ Ki-67(+) cells was related to a higher malignant potential. We conclude the nuclear morphology is related to cell differentiation represented by CK expression and cell proliferative activity. [ABSTRACT FROM AUTHOR]

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2-), luminal B (ER or PR+HER2+), HER2 overexpressing (ER-PR-HER2+), triple-negative (ER-PR-HER2-), basal-like (ER-PR-HER2-CK5+), non-classified (ER-PR-HER2-CK5-) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2- luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers. [ABSTRACT FROM AUTHOR]

For primary bladder tumors, distinguishing urothelial carcinoma (UC) invading the fibromuscular stroma of the prostate (pT4a) from in situ UC involving prostatic ducts can be difficult. Immunohistochemical markers (cytokeratin [CK]5/6, CK5, CK7, CK20, p53, p63, high-molecular-weight keratin [HMWK], androgen receptor, prostate-specific antigen [PSA], prostate specific acid phosphatase [PSAP], laminin, CD44s, CD141) were assessed for their usefulness in determining depth of UC invasion in the prostate. In cystoprostatectomy specimens containing in situ UC in prostatic ducts, both CK5/6 and CK5 clearly differentiated prostatic basal cells from in situ UC. The remaining markers were not effective in determining depth of tumor invasion. Double-stain combinations CK7/CK5 and p5 3/CK5 were performed and robustly color contrasted in situ tumor from surrounding basal cells. The use of CK5/6, CK5, CK7/CK5, or p53/CK5 is recommended to assist in determining the depth of UC invasion in the prostate when histologic findings are equivocal. [ABSTRACT FROM AUTHOR]

Background: The distinction of lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has important therapeutic implications. Napsin A is a recently developed marker, which has shown high specificity for lung tissue in the surgical pathology specimens. In this study, we have evaluated whether the use of a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually with relatively scant microfragments of diagnostic material. Materials and Methods: Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were studied. All these cases had subsequently confirmed diagnosis in biopsies or resection specimens. The sections were immunostained with two color methods of TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous / cytoplasmic CK5 staining were interpreted as 'positive'. Results: All 20 FNA cell blocks from SCC cases were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC cases were positive with dual stain of TTF-1 + Napsin A and negative for dual stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 + Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the seven PDC cases, five cases that were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and negative for dual stain p63 + CK5, consistent with ADC. Conclusions: Simultaneous coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5 in SCC demonstrated high sensitivity and specificity. The panel with multiplex Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for evaluation of FNA specimens with relatively scant cellularity. [ABSTRACT FROM AUTHOR]

The expression of basal cytokeratin markers CK5/6 in breast carcinomas has been associated with high histological grade and poor clinical outcome. A previous study has shown that CK5/6 can be detected in up to 17% of invasive lobular carcinomas (ILC). Here we study the expression of three basal cytokeratin markers (CK5/6, CK14, and CK17) in 53 ILC cases diagnosed by histology and lack of E-cadherin expression. Among them, 42 were classic lobular carcinomas, 6 were tubular-lobular carcinoma, and 5 were pleomorphic lobular carcinomas. There was no significant difference among these three groups in patients' age, tumor size, uni- and multi-focality, expression of ER and PR, lymphovascular invasion, perineural invasion and lymph node metastasis. The only statistically different factor was HER2 over-expression, which was observed only in pleomorphic ILC (P = 0.0073). None of the 53 cases expressed CK5/6, CK14 or CK17; and 51/53 cases expressed luminal markers CK8 and CK18, and the two negative cases were both classic lobular carcinoma, with positivity for ER and PR. In conclusion, all 53 cases of ILC failed to show expression by any of the three basal CK markers, suggesting that very few ILC will demonstrate a basal phenotype when assessed by immunohistochemistry (IHC). More studies are needed to investigate molecular classification in lobular carcinoma of the breast. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates, in a reactive manner, all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by LysoTracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial LysoTracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s that behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expressed AEC2 and basal cell markers, resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of LysoTracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5, and CD24 expression in human lung epithelial cells. Combining functional analysis with extracellular and intracellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis. [ABSTRACT FROM AUTHOR]

Aims: To assess the expression of cytokeratin (CK) 5/6 in bilateral breast cancers and to assess the relationship between its expression and other prognostic variables, as well as between CK5/6 expression and patients' survival. Methods and results: The expression of CK5/6, PTEN protein, oestrogen receptor, progesterone receptor, p53 and c-erbB-2 protein were evaluated by immunohistochemistry in 88 primary breast cancers diagnosed in 44 women. To assess the prognostic value of studied factors, Cox regression analysis was performed. Expression of CK5/6 was found in 23 of 88 primary breast carcinomas (23/88; 26%). The hazard ratio of development of distant metastasis in patients in whom at least one cancer was CK5/6+ was 99.8 ( P = 0.037) and in patients with at least one carcinoma with reduced PTEN expression it was 10.8 ( P = 0.044). CK5/6 expression was correlated with absence of oestrogen ( P < 0.0001) and progesterone receptors ( P < 0.0001) and very strong expression of p53 ( P < 0.05). Reduced PTEN expression was correlated with presence of axillary metastases ( P < 0.01), with very strong expression of c-erbB-2 ( P < 0.05) and with reduced expression of oestrogen receptor ( P < 0.05). Conclusions: Analysis of expression of CK5/6 and PTEN protein in bilateral breast carcinomas may be of value in clinical practice and warrant further studies. [ABSTRACT FROM AUTHOR]

Molecular subtyping of urothelial carcinoma (UC) is similar to that of breast cancer and is based on the developmental biology approach. The aim of the present study is to assess the prognostic impact of CK5, CK14, and CK20 expression in urinary bladder cancer (UBC) with the potential to stratify them into different subtypes. The current study examined the immunohistochemical expression of CK5, CK14, and CK20 in 90 specimens of UBC. CK5 was expressed in 81.1% of the cases and was significantly associated with old age, muscle invasion, presence of bilharziasis, and tendency for poor overall survival. CK20 was expressed in 47.8% of the cases and was associated with nonmuscle invasion and pure UC while 50% of the cases expressed CK14 that were associated with muscle invasion and perineural invasion. Most squamous cell carcinoma and those associated with bilharziasis were belonged to Ck5+/CK20- subgroup while pure UC and those lacked bilharziasis were located in the Ck5+/CK20+ subgroup. The basal group (Ck5+/CK14+/CK20-) showed high proliferative features compared to the intermediate group (Ck5+/CK14-/CK20-). Generally, presence of CK5 is associated with adverse features especially in the group lacking CK20; however, basal and intermediate subgroups share CK5 expression but they show different proliferative capacities, so their distinction by CK14 is helpful.

Background: The potentially curative and/or palliative therapy for non-resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub-typing of non-small cell lung carcinoma (NCSLC) has become paramount., Objectives: As there are few data from South Africa, we aimed to determine utility of TTF-1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin-fixed paraffin-embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas., Methods: All cases of NSCLC diagnosed during a 3-year period were retrospectively identified. All FNA biopsy and formalin-fixed paraffin-embedded cases that were stained with TTF-1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data., Results: We included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF-1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF-1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma., Conclusion: All four immunostaining methods had high sensitivities. TTF-1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF-1. The specificity of CK5 for squamous cell carcinoma was higher than p63., (© 2019 John Wiley & Sons Ltd.)