Prognostic values of molecular subtypes and SWI/SNF protein expression in de-differentiated/undifferentiated endometrial carcinoma.

Aims: Classification and risk stratification of endometrial carcinoma (EC) has transitioned from histopathological features to molecular classification, e.g. the ProMisE classifier, identifying four prognostic subtypes: POLE mutant (POLEmut) with almost no recurrence or disease-specific death events, mismatch repair deficient (MMRd) and no specific molecular profile (NSMP), with intermediate outcome and p53 abnormal (p53abn) with poor outcomes.

Papillary and ductal patterns of mesonephric-like adenocarcinomas are often overlooked: a retrospective revaluation of over 1000 endometrial carcinomas.

Aims: Mesonephric-like adenocarcinoma (MLA) of the endometrium is often a diagnostic challenge, due to its morphological resemblance to other more common Müllerian neoplasms. This study aimed to retrospectively identify overlooked MLA in a large endometrial carcinoma cohort, using a combination of immunohistochemistry (IHC), morphology and KRAS sequencing.

Methods And Results: IHC was conducted on 1094 endometrial carcinomas, identifying 16 potential MLA cases based on GATA3+ and/or TTF1+ and ER- staining patterns, which subsequently underwent detailed histological review, KRAS sequencing and ProMisE molecular classification.

Interpretation of p16 and p53 in the Classification of Squamous Cell Carcinoma of the Vulva-An Interobserver Agreement Study.

Squamous cell carcinoma of the vulva (vSCC) is currently categorized either as human papillomavirus (HPV) associated or independent. Immunohistochemical stains, p16 INK4a (p16) and p53 are helpful biomarkers to support the designation of vSCC into 1 of the 3 tumor pathways: (1) HPV-associated, (2) HPV-independent, TP53 mutant, or (3) HPV-independent, TP53 wild type. Recently, a framework of p53 expression patterns in vSCC was proposed.

Typing of Vulvar Squamous Cell Carcinoma: Why it is Important?

The classification of vulvar squamous cell carcinoma (VSCC), as in endometrial cancer, has shifted from the histology-based descriptors toward molecular-based identifiers. Recently, it has been reported that there are 3 genetically distinct and clinically significant subtypes of VSCC: HPV-associated VSCC, HPV-independent/p53 wild-type VSCC, and HPV-independent/p53-mutated VSCC. Each group has different prognostic implications as well as response to treatment, thus reinforcing the need for this 3-tier molecular classification.

Abnormal p53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery.

Most (60%-80%) of the oral cavity invasive squamous cell carcinoma (OSCC) demonstrate molecular alterations in TP53. The presence of TP53 mutations in multiple organ systems has been associated with a more aggressive clinical course. This study aimed to classify OSCC into p53 wild-type OSCC and p53-abnormal OSCC using p53 immunohistochemistry and to determine if abnormal p53 status correlates with a higher risk of lymph node metastasis at the time of surgery.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

Objective: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen.

Methods: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate.

Endometrial Carcinosarcomas are Almost Exclusively of p53abn Molecular Subtype After Exclusion of Mimics.

Our aim was to assess the molecular subtype(s) and perform a detailed morphologic review of tumors diagnosed as carcinosarcoma in a population-based cohort. Forty-one carcinosarcomas were identified from a cohort of 973 endometrial carcinomas diagnosed in 2016. We assessed immunostaining and sequencing data and undertook expert pathology reviews of these cases as well as all subsequently diagnosed (post-2016) carcinosarcomas of no specific molecular profile (NSMP) molecular subtype (n=3) from our institutions.

Utilization of p53 and p16 Immunohistochemistry in the Classification of Human Papillomavirus-Associated, p53 Wild-Type, and p53 Abnormal Oral Epithelial Dysplasia.

p53 immunohistochemistry (IHC) has recently been shown to be a clinically useful marker for predicting risk of progression to invasive squamous cell carcinoma in oral epithelial dysplasia (OED). The literature supports the use of p53 IHC as a marker to identify TP53 mutation in in situ and invasive vulvar lesions and as a surrogate marker for high-risk human papillomavirus (HPV) infection, but there is little documentation for similar use in OED. The purpose of this study was to determine whether p53 IHC is a reliable surrogate marker for detecting both TP53 mutation and high-risk HPV infection in OED.

Abnormal p53 Immunohistochemical Patterns Shed Light on the Aggressiveness of Oral Epithelial Dysplasia.

The diagnosis of oral epithelial dysplasia is based on the degree of architectural and cytologic atypia in the squamous epithelium. The conventional grading system of mild, moderate, and severe dysplasia is considered by many the gold standard in predicting the risk of malignant transformation. Unfortunately, some low-grade lesions, with or without dysplasia, progress to squamous cell carcinoma (SCC) in short periods.

p53-Abnormal "Fields of Dysplasia" in Human Papillomavirus-Independent Vulvar Squamous Cell Carcinoma Impacts Margins and Recurrence Risk.

Abnormal p53 (p53abn) immunohistochemical (IHC) staining patterns can be found in vulvar squamous cell carcinoma (VSCC) and differentiated vulvar intraepithelial neoplasia (dVIN). They can also be found in the adjacent skin that shows morphology that falls short of the traditional diagnostic threshold for dVIN. Vulvectomy specimens containing human papillomavirus-independent p53abn VSCC with margins originally reported as negative for invasive and in situ disease were identified.

Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions by p16 and p53 Immunohistochemistry: Considerations, Caveats, and an Algorithmic Approach.

There is emerging evidence that vulvar squamous cell carcinoma (VSCC) can be prognostically subclassified into 3 groups based on human papillomavirus (HPV) and p53 status: HPV-associated (HPV+), HPV-independent/p53 wild-type (HPV-/p53wt), or HPV-independent/p53 abnormal (HPV-/p53abn). Our goal was to assess the feasibility of separating VSCC and its precursors into these 3 groups using p16 and p53 immunohistochemistry (IHC). A tissue microarray containing 225 VSCC, 43 usual vulvar intraepithelial neoplasia (uVIN/HSIL), 10 verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN), and 34 differentiated VIN (dVIN), was stained for p16 and p53.

Villoglandular Pattern in HPV-associated Endocervical Adenocarcinoma is Associated With Excellent Prognosis: A Reappraisal of 31 Cases Using IECC and Silva Pattern Classification.

Villoglandular adenocarcinoma of the cervix is a rare histologic entity that typically develops in young women, characterized by an association with oral contraceptives and excellent prognosis, though this point is controversial. These tumors have not been studied in the context of the International Endocervical Adenocarcinoma Criteria and Classification (IECC) or Silva Pattern Classification. We analyzed 31 cases that met strict diagnostic criteria, including being completely excised with negative margins.

Data Set for the Reporting of Carcinomas of the Vulva: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

A cogent and comprehensive pathologic report is essential for optimal patient management, cancer staging, and prognostication. This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the vulval carcinoma reporting data set. It describes the "core" and "noncore" elements to be included in pathology reports for vulval carcinoma, inclusive of clinical, macroscopic, microscopic, and ancillary testing considerations.

Significance of p53 and presence of differentiated vulvar intra-epithelial neoplasia (dVIN) at resection margin in early stage human papillomavirus-independent vulvar squamous cell carcinoma.

Objective: Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas.

Methods: Patients with stage I-II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included.

Cervical Adenosquamous Carcinoma: Detailed Analysis of Morphology, Immunohistochemical Profile, and Outcome in 59 Cases.

Although both the 2014 and 2020 World Health Organization (WHO) criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma (ASC), in practice, ASC diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphologic, and clinical features and outcomes associated with ASCs, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed ASCs (including glassy cell carcinoma and related lesions) to confirm an ASC diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation.

The proteome of clear cell ovarian carcinoma.

Clear cell ovarian carcinoma (CCOC) is the second most common subtype of epithelial ovarian carcinoma. Late-stage CCOC is not responsive to gold-standard chemotherapy and results in suboptimal outcomes for patients. In-depth molecular insight is urgently needed to stratify the disease and drive therapeutic development.

Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique.

Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Squamous and Glandular Lesions of the Vulva and Vagina: What's New and What Remains Unanswered?

A number of changes have been introduced into the 5th Edition of the World Health Organization (WHO) Classification of squamous and glandular neoplasms of the vulva and vagina. This review highlights the major shifts in tumor classification, new entities that have been introduced, recommendations for p16 immunohistochemical testing, biomarker use, molecular findings and practical points for pathologists which will affect clinical care. It also touches upon several issues that still remain answered in these rare but undeniably important women's cancers.

Data Set for the Reporting of Carcinomas of the Vagina: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Primary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International Collaboration on Cancer Reporting (ICCR) is developing standardized, evidence-based reporting data sets for multiple cancer sites. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary vaginal carcinomas and present the core and noncore data elements with explanatory commentaries.

HPV-independent, p53-wild-type vulvar intraepithelial neoplasia: a review of nomenclature and the journey to characterize verruciform and acanthotic precursor lesions of the vulva.

Vulvar squamous cell carcinomas and their precursors are currently classified by the World Health Organization based on their association with high-risk human papillomavirus (HPV). HPV independent lesions often harbor driver alterations in TP53, usually seen in the setting of chronic vulvar inflammation. However, a group of pre-invasive vulvar squamous lesions is independent from both HPV and mutant TP53.

The impact of whole genome and transcriptome analysis (WGTA) on predictive biomarker discovery and diagnostic accuracy of advanced malignancies.

In this study, we evaluate the impact of whole genome and transcriptome analysis (WGTA) on predictive molecular profiling and histologic diagnosis in a cohort of advanced malignancies. WGTA was used to generate reports including molecular alterations and site/tissue of origin prediction. Two reviewers analyzed genomic reports, clinical history, and tumor pathology.