Comprehensive immunohistochemical analysis of the gastrointestinal and Müllerian phenotypes of 139 ovarian mucinous cystadenomas

Halimi, Sultan Ahmad; Maeda, Daichi; Ushiku-Shinozaki, Aya; Goto, Akiteru; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki; Ushiku, Tetsuo; Fukayama, Masashi

doi:10.1016/j.humpath.2020.11.011

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…8 Halimi et al recently showed, using a combination of gastric, intestinal and M€ ullerian markers, that 93% of mucinous cystadenomas exhibited gastrointestinal differentiation, with 6% exhibiting a pure M€ ullerian phenotype; some tumours exhibited intermediate features. 25 In practice, when reporting these neoplasms, it is not necessary to distinguish between gastrointestinal and M€ ullerian-type epithelium. Typically, the glandular epithelium has basally orientated, small uniform nuclei exhibiting minimal or no mitotic activity.…”

Section: Mucinous Carcinoma Arising In Teratomamentioning

confidence: 99%

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach

2021

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Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approachThe morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad, and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the World Health Organisation (WHO) Classification of female genital tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intra-operative handling of these tumours. A number of diagnostic issues remain unresolved, highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia.

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Section: Mucinous Carcinoma Arising In Teratomamentioning

confidence: 99%

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach

2021

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“…9 Therefore, membranous CLDN18 is considered to be a highly selective immunohistochemical marker to detect gastric differentiation in pancreatobiliary, 10 colorectal, 11 and ovarian mucinous neoplasms. 9,12 The CLDN family comprises at least 27 transmembrane proteins that are the main components of tight junctions (TJs). CLDNs generally localize to the apical and basolateral regions of the cell membrane and play an important role in cell-cell adhesion, maintenance of cell polarity and selective paracellular permeability, regulating epithelialmesenchymal transformation (EMT), cell proliferation, migration and infiltration in cancer.…”

Section: Introductionmentioning

confidence: 99%

“…CLDN18 is expressed along the basolateral membrane in all types of differentiated gastric epithelial cells, including surface mucous cells, chief cells, parietal cells, and endocrine cells 9 . Therefore, membranous CLDN18 is considered to be a highly selective immunohistochemical marker to detect gastric differentiation in pancreatobiliary, 10 colorectal, 11 and ovarian mucinous neoplasms 9,12 …”

Section: Introductionmentioning

confidence: 99%

Membranous and nuclear staining of CLDN18 in HPV‐independent and HPV‐associated endocervical adenocarcinomas

et al. 2022

Cancer Medicine

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Objectives: A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features. Methods:We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed. Results: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001). Conclusion:Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new

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“…Primary ovarian mucinous tumors are thought to progress stepwise from cystadenomas, to mucinous borderline tumors/atypical proliferative mucinous tumors (MBT/APMT), and to intraepithelial and/or invasive carcinomas, representing a biological continuum in the sequence of carcinogenesis [ 1 , 2 , 3 ]. Although studies have shown that most epithelial ovarian tumors develop from Müllerian-derived precursors, ovarian mucinous tumors typically lack a Müllerian phenotype [ 4 , 5 , 6 , 7 ]. It has been postulated that a portion of mucinous tumors are derived from Brenner tumors or teratomas and molecular studies have indicated a clonal relationship to support this hypothesis [ 6 , 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Mucinous Borderline Tumor Associated with Mesonephric-like Proliferation: Further Evidence for a Possible New Origin of Ovarian Mucinous Neoplasms

et al. 2022

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Some ovarian mucinous tumors are thought to originate from Brenner tumors and teratomas; however, data are limited on what could be the origin for the remaining tumors. We report a new case of ovarian mucinous borderline tumor/atypical proliferative mucinous tumor (MBT/APMT) co-existing with a mesonephric-like proliferation (MLP)/mesonephric-like hyperplasia (MLH). The patient was a 58-year-old woman who presented with a pelvic mass and abdominal pain. Pathology demonstrated an 11 cm MBT/APMT in the left ovary. In addition, the tumor contained one focal area (<1% of total tumor volume) of MLP/hyperplasia adjacent to, or intimately admixed with, mucinous epithelium, with an immunophenotype of diffuse Pax8 and Gata3 expression and negative TTF-1, ER, and PR staining. Pax8 was also weakly positive in the MBT/APMT component. Some mesonephric-like glands partially exhibited gastrointestinal-type mucinous metaplasia/differentiation. A polymerase chain reaction (PCR)-based Sanger sequencing demonstrated that a KRAS G12V mutation was present in both MLP/MLH and MBT/APMT components, providing further evidence to support their clonal relationship. We previously reported a series of similar cases and demonstrated a novel association between MLP, mesonephric-like adenocarcinoma and ovarian mucinous tumor. It is conceivable that benign MLPs may have ability to differentiate to lineage-specific mucinous lesions, and, as such, they may serve as a possible new origin of some ovarian mucinous neoplasms; in particular, Pax8-positive tumors. The current case provides additional evidence to support this theory.

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Comprehensive immunohistochemical analysis of the gastrointestinal and Müllerian phenotypes of 139 ovarian mucinous cystadenomas

Cited by 11 publications

References 30 publications

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach

Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach

Membranous and nuclear staining of CLDN18 in HPV‐independent and HPV‐associated endocervical adenocarcinomas

Mucinous Borderline Tumor Associated with Mesonephric-like Proliferation: Further Evidence for a Possible New Origin of Ovarian Mucinous Neoplasms

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