Membranous and nuclear staining of <scp>CLDN18</scp> in <scp>HPV</scp>‐independent and <scp>HPV</scp>‐associated endocervical adenocarcinomas

Du, Xiuzhen; Hu, Yanjiao; Ji, Xiaoyu; Sui, Lei; Zheng, Qinghe; Song, Kejuan; Lv, Teng; Chen, Yulong; Zhao, Han; Dai, Sheng; Zhao, Peng; Yao, Qing

doi:10.1002/cam4.5029

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…Of note is the CLDN18 claudin gene which showed a generally high level of over-expression. High CLDN18 expression was recently reported in certain cervical adenocarcinomas [ 34 ]. Here, we show that it is generally over-expressed in all endometrial cancers, which agrees with previous conclusions [ 34 ] that it could serve as a molecular marker for ECs.…”

Section: Resultsmentioning

confidence: 99%

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms

Stan,

Bosart,

Kaur

et al. 2024

PLoS ONE

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Analyzed endometrial cancer (EC) genomes have allowed for the identification of molecular signatures, which enable the classification, and sometimes prognostication, of these cancers. Artificial intelligence algorithms have facilitated the partitioning of mutations into driver and passenger based on a variety of parameters, including gene function and frequency of mutation. Here, we undertook an evaluation of EC cancer genomes deposited on the Catalogue of Somatic Mutations in Cancers (COSMIC), with the goal to classify all mutations as either driver or passenger. Our analysis showed that approximately 2.5% of all mutations are driver and cause cellular transformation and immortalization. We also characterized nucleotide level mutation signatures, gross chromosomal re-arrangements, and gene expression profiles. We observed that endometrial cancers show distinct nucleotide substitution and chromosomal re-arrangement signatures compared to other cancers. We also identified high expression levels of the CLDN18 claudin gene, which is involved in growth, survival, metastasis and proliferation. We then used in silico protein structure analysis to examine the effect of certain previously uncharacterized driver mutations on protein structure. We found that certain mutations in CTNNB1 and TP53 increase protein stability, which may contribute to cellular transformation. While our analysis retrieved previously classified mutations and genomic alterations, which is to be expected, this study also identified new signatures. Additionally, we show that artificial intelligence algorithms can be effectively leveraged to accurately predict key drivers of cancer. This analysis will expand our understanding of ECs and improve the molecular toolbox for classification, diagnosis, or potential treatment of these cancers.

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Section: Resultsmentioning

confidence: 99%

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms

Stan,

Bosart,

Kaur

et al. 2024

PLoS ONE

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“…24 One study showed membranous claudin-18 expression in all gastric-type cervical adenocarcinomas tested (eight of eight cases), but also in a subset of other cervical adenocarcinomas, both HPV-associated and HPV-independent (20 of 52 cases), particularly those with intestinal-type differentiation (five of nine cases positive). 25 This marker also shows potential as a therapeutic target. 25 It can be summarised that, although a combination of markers may help establish gastric differentiation, no marker is totally sensitive or specific and a single reliable marker of gastric differentiation has not yet been identified.…”

Section: Gastric-type Adenocarcinomamentioning

confidence: 99%

“…25 This marker also shows potential as a therapeutic target. 25 It can be summarised that, although a combination of markers may help establish gastric differentiation, no marker is totally sensitive or specific and a single reliable marker of gastric differentiation has not yet been identified.…”

Section: Gastric-type Adenocarcinomamentioning

confidence: 99%

“…Claudin‐18, an adhesion molecule expressed in the cytoplasmic membrane of normal and neoplastic gastric epithelium, has also shown promise in separating gastric‐type adenocarcinoma from other cervical adenocarcinomas, with superior sensitivity to TFF2 and HIK1083 and more frequent diffuse staining 24 . One study showed membranous claudin‐18 expression in all gastric‐type cervical adenocarcinomas tested (eight of eight cases), but also in a subset of other cervical adenocarcinomas, both HPV‐associated and HPV‐independent (20 of 52 cases), particularly those with intestinal‐type differentiation (five of nine cases positive) 25 . This marker also shows potential as a therapeutic target 25 .…”

Section: What Defines a Gastric‐type Lesion: Morphology And Immunophe...mentioning

confidence: 99%

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Gastric‐type glandular lesions of the female genital tract excluding the cervix: emerging pathological entities

Wong,

Talia,

McCluggage

2024

Histopathology

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In the last two decades or so, a spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation has been described, with gastric‐type adenocarcinoma representing the most common human papillomavirus (HPV)‐independent cervical adenocarcinoma. More recently, limited literature has reported a variety of gastric‐type glandular lesions at other sites within the female genital tract and, as in the cervix (the most common site for these lesions), a spectrum of benign, premalignant and malignant lesions has been proposed. We provide an update and review of the emerging spectrum of gastric‐type glandular lesions at female genital tract sites other than the cervix. In the endometrium, putative gastric‐type glandular lesions include mucinous metaplasia of gastric‐type, atypical mucinous proliferation of gastric‐type and gastric‐type adenocarcinoma. Similarly in the vagina, gastric‐type adenosis, atypical adenosis and adenocarcinoma have been described. There have also been occasional reports of gastric‐type lesions involving the ovary and fallopian tube. We provide guidance on how to recognise gastric‐type lesions morphologically and immunophenotypically and stress that sometimes these lesions occur at more than one site within the female genital tract (synchronous/multifocal gastric‐type lesions of the female genital tract), sometimes in association with Peutz–Jeghers syndrome.

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

Cited by 5 publications

References 33 publications

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms

Detection of driver mutations and genomic signatures in endometrial cancers using artificial intelligence algorithms

Gastric‐type glandular lesions of the female genital tract excluding the cervix: emerging pathological entities

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

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