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Molecular Mediator of Prostate Cancer Progression and Its Implication in Therapy
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Samikshan Dutta, Navatha Shree Sharma, Ridwan Islam, Kaustubh Datta
Majority of the prostate cancers are pathologically classified as adenocarcinoma with luminal prototype. It is diagnosed by the absence of the basal cell markers like cytokeratin 5/14 and p63 and elevated luminal proteins such as AR and a-methylacyl-CoA racemase [35–38]. Other subtypes of prostate cancers like ductal adenocarcinoma, neuroendocrine prostate cancer, mucinous carcinoma, and signet ring carcinoma account for very low percentage [39–42].
Lung Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Squamous cell carcinoma (SCC) now accounts for up to 30% of patients diagnosed with NSCLC in Western countries, occurring usually in men and typically related to smoking. Historically, these tumors were stereotypically found proximally in the major bronchi, but increasing numbers are now found more peripherally. Macroscopically, these tumors appear as firm lesions with a pale-grey, gritty surface and can be cavitating. Microscopically, the hallmarks of squamous differentiation are apparent, with prominent intercellular bridges and keratinization. Immunohistochemical staining with antibodies against cytokeratin 5, 6, p40, and p63 increases confidence in the diagnosis. Molecularly, SCC has been shown to demonstrate recurrent mutations in 11 genes, including mutation of TP53 in almost all sampled cases. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumors.6 None of these commonest mutations in SCC are currently targetable.
Thyroid and Parathyroid Gland Pathology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Ram Moorthy, Sonia Kumar, Adrian T. Warfield
SCNs comprise irregularly shaped clusters of interfollicular cells delineated by basal lamina. The dominant cell component (main cell) comprises polygonal to fusiform cells disposed in solid array sometimes with an epidermoid appearance, though generally non-keratinizing and devoid of intercellular bridges (prickles). They less commonly show a glandular morphology and may paradoxically be microcystic, micropapillary and/or mucinous. SCNs co-express cytokeratins, carcinoembryonic antigen (CEA, CD66e), galectin-3 and many pan-neuropeptides such as chromogranin A, synaptophysin and somatostatin, but they are negative for markers of terminal differentiation, viz. thyroglobulin (Tg), thyroid transcription factor-1 (TTF-1) and calcitonin (Figure 58.4). They also contain a minor subpopulation of C-cells, which show a partially differentiated immunophenotype. SCNs consistently stain for p63, a homologue of p53, a nuclear transcription factor that induces expression of cytokeratin 5 (CK5) and cytokeratin 14 (CK14). The gene for p63 is universally expressed in basal cells of stratified epithelia and plays a major role in triggering the maturation of these into squamous epithelium.
Hypoxic conditions promote a proliferative, poorly differentiated phenotype in COPD lung tissue progenitor cells in vitro
Published in Experimental Lung Research, 2023
Tina P. Dale, Michael D. Santer, Mohammed Haris, Wei Zuo, Nicholas R. Forsyth
The in vitro growth of cells from the lungs is reliant on the expansion of a progenitor cell population; in vivo these populations are responsible for tissue repair, cellular homeostasis, and thus function. Typically, respiratory progenitor cells are TP63 and cytokeratin 5 positive, identifying progenitor cell types from both the proximal (basal cells) and more distal airways with further variation occurring in sub-populations of these cells.28,29 We observed culture heterogeneity with widespread cytokeratin 5 positivity but more limited TP63 expression, with the TP63 positive cell fraction larger, both at isolation and following expansion in 2% O2. Zhao et al have described a cytokeratin 5 positive/TP63 negative population arising from double positive cells following engraftment in a bleomycin-injured mouse lung model,30 suggesting that reduced oxygen may be inhibiting lineage progression in our cultures. Inhibition of the differentiation of cytokeratin 5 progenitors consequently impairs alveolar epithelial barrier formation,30 something that we also observed, with reduced ALI TEER in 2% cultured cells.
Expression of markers of stem cell characteristics, epithelial-mesenchymal transition, basal-like phenotype, proliferation, and androgen receptor in metaplastic breast cancer and their prognostic impact
Published in Acta Oncologica, 2021
Sari Voutilainen, Päivi Heikkilä, Mika Sampo, Heli Nevanlinna, Carl Blomqvist, Johanna Mattson
The most striking finding of the present study was the strong prognostic effect of the expression of a basal-like phenotype according to cytokeratin 5/6 or EGFR-expression. The prognosis was excellent in the 15% of cases not expressing this phenotype since no patients experienced a relapse in this group. The result is supported by a recent study by McCart Reed et al. where EGFR-expression, large tumor size, and mixed MpBC histological subtype were significant indicators of poor prognosis [14]. However, the expression of CK 5/6 was not prognostic in this study. The results of other biomarker studies in MpBC have been variable. A small study of EMT-markers in MpBc (n = 13), including vimentin, and the EMT-inducer ZEB1 found ZEB1 to be an independent prognostic factor for poor DFS [15]. In a study of 55 cases, Song et al. showed that high Ki-67 (>14%) and the clinical stage were significantly associated with disease-free survival in MpBC [2]. The prognostic implication of proliferation rate was confirmed in the present study, although the p-value did not reach the pre-defined significance level due to correction for multiple testing.
The value of desmosomal plaque-related markers to distinguish squamous cell carcinoma and adenocarcinoma of the lung
Published in Upsala Journal of Medical Sciences, 2020
Inmaculada Galindo, Mercedes Gómez-Morales, Inés Díaz-Cano, Álvaro Andrades, Mercedes Caba-Molina, María Teresa Miranda-León, Pedro Pablo Medina, Joel Martín-Padron, María Esther Fárez-Vidal
Immunohistochemistry is widely used for the subtyping of lung carcinomas. Thyroid transcription factor 1 (TTF1) (26) and Napsin A (27) are considered the most useful markers for AC diagnosis, and evaluation of the former is considered easier because it is a nuclear marker. Although cytokeratin 7 (CK7) has also been used as a marker of AC (28), its usefulness is not universally accepted (2). Cytokeratin 5/6 (CK5/6), p63, and p40 are recommended markers for SCC (28,29), while DSG3 and desmocollin 3 have also emerged as potential SCC markers, although their clinical value has yet to be established (25,30,31). However, despite the efficacy of these markers, numerous confirmed lung carcinoma cases are either positive for both AC and SCC markers (double-positive) or negative for one or the other type of marker (32). Given the more stringent requirements for the histologic classification of lung cancers, an antibody panel is required that definitively differentiates AC from SCC. A particular challenge is posed by poorly differentiated tumours and by samples with the technical artefacts frequently encountered in small biopsy specimens, which are the only available tissue samples from patients in advanced stages.