A comparison of p53 and <scp>WT</scp>1 immunohistochemical expression patterns in tubo‐ovarian high‐grade serous carcinoma before and after neoadjuvant chemotherapy

Casey, Laura; Köbel, Martin; Ganesan, Raji; Tam, Simone; Prasad, Rajeev; Böhm, Steffen; Lockley, Michelle; Jeyarajah, Arjun; Brockbank, Eleanor; Faruqi, Asma; Gilks, C. Blake; Singh, Naveena

doi:10.1111/his.13272

Cited by 28 publications

(20 citation statements)

References 21 publications

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“…In this study, we confirmed the presence of TP53 mutations in HGSC showing a wild-type p53 immunostaining pattern and demonstrated the mutational constancy between matched pre-and post-chemotherapeutic HGSC tissue samples. This result is not only concordant with a previous study reporting pre-and post-chemotherapeutic p53 expression in HGSC using only immunohistochemistry (40), but also presents confirmatory evidence via NGS. Our data suggest that similar p53 immunoexpression patterns in preand post-chemotherapeutic samples indicate the presence of the same TP53 mutation.…”

Section: Discussionsupporting

confidence: 92%

“…Although a certain number of HGSC cases show wild-type pattern of p53 immunostaining, there have been a few studies showing that, when sequenced, all HGSC cases examined actually bear TP53 mutations (9,15). Considering that p53 immunopositivity is determined by an immunohistochemical staining pattern that correlates with TP53 mutation as opposed to simply a positive or negative staining and that some HGSC cases with truncating or splice site TP53 mutations can show a non-functional p53 expression pattern, the fact that p53 immunostaining cannot accurately predict TP53 mutational status is understandable (40,41). There are two main chemotherapeutic treatment methods for managing ovarian carcinomas, including HGSC: 1) PDS followed by postoperative platinum-based adjuvant chemotherapy and 2) neoadjuvant chemotherapy followed by IDS.…”

Section: Discussionmentioning

confidence: 99%

“…There are two main chemotherapeutic treatment methods for managing ovarian carcinomas, including HGSC: 1) PDS followed by postoperative platinum-based adjuvant chemotherapy and 2) neoadjuvant chemotherapy followed by IDS. The morphology of post-chemotherapeutic carcinoma is in vivo 33: 1485-1492 (2019) 1488 different from its pretreatment appearance, making histological subtyping and grading difficult (40). Meanwhile, despite the tremendous genomic diversity that develops at very early stages of carcinogenesis (42), ancestral clones persist, irrespective of disease progression and chemotherapeutic intervention (43).…”

Section: Discussionmentioning

confidence: 99%

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Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Kim

Woo

et al. 2019

In Vivo

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Kim

Woo

et al. 2019

In Vivo

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“…After constructing the tissue microarray, the samples were stained for O -GlcNAcylation (RL2) and OGT. The intensity of the staining was scored using the H-score method (3D HISTECH, H-SCORE = ∑(PI × I) = (percentage of cells of weak intensity × 1) + (percentage of cells of moderate intensity × 2) + (percentage of cells of strong intensity × 3) [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

et al. 2018

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BackgroundThis study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer.MethodsImmunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP–LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown.ResultsThe expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum.ConclusionsThe data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.

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“…It has been shown that immunohistochemical expression of WT1 in HGSC is largely concordant before and after chemotherapy, although generalised diminution of nuclear immunoreactivity has been noted in post-treatment tumours 64. Diffuse immunoreactivity with p16 is usually seen in HGSC,65 66 and ER positivity is also commonly seen 67 68.…”

Section: Pathological Examination Of Post-nact Specimensmentioning

confidence: 99%

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

McCarthy¹,

Rouzbahman²,

Thiryayi³

et al. 2019

J Clin Pathol

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In recent times, there has been a growing tendency to treat advanced gynaecological malignancies with neoadjuvant chemotherapy (NACT), with the goal of reducing tumour volume and enhancing operability resulting in optimal cytoreduction. This approach is used in particular for patients with advanced high-grade serous carcinoma of the ovary, fallopian tube or peritoneum. Pathology plays a crucial role in the management of these patients, both before and after NACT. Prior to initiation of NACT, a biopsy should be performed, usually of the omental cake, to confirm that a malignancy is present, to identify the site of origin of the tumour and to type and grade the tumour. Histopathologists must be aware of the resultant morphological effects of NACT when examining specimens following interval cytoreduction surgery. Tumour typing and grading, and even the identification of residual neoplasia, are particular challenges. Immunohistochemistry, when used judiciously, can be a useful adjunct in certain scenarios. A pathological assessment of the response to chemotherapy, and the pathological stage should be provided in the pathology report, as these may inform prognosis and subsequent management. We present a comprehensive overview of the relevant clinical and pathological aspects pertaining to NACT for gynaecological malignancies for the practicing surgical pathologist.

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A comparison of p53 and WT1 immunohistochemical expression patterns in tubo‐ovarian high‐grade serous carcinoma before and after neoadjuvant chemotherapy

Cited by 28 publications

References 21 publications

Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

Suppressed OGT expression inhibits cell proliferation while inducing cell apoptosis in bladder cancer

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know

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