Invasive stratified mucin‐producing carcinoma (ISMC) of the cervix: a clinicopathological and molecular analysis of 59 cases with special emphasis on histogenesis and potential therapeutic targets

Author:

Yao Yeli1,Wang Yan2,Ye Lei2,Lu Bingjian3ORCID,Lu Weiguo4

Affiliation:

1. Department of Gynecologic Oncology Women's Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang Province China

2. Department of Surgical Pathology Women's Hospital, School of Medicine Zhejiang University Hangzhou Zhejiang Province China

3. Department of Surgical Pathology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang Province China

4. Department of Gynecologic Oncology, Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Women's Reproductive Health Laboratory of Zhejiang Province Women's Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang Province China

Abstract

AimsThis study aimed to better characterize the clinical and molecular features in invasive stratified mucin‐producing carcinoma (ISMC), an uncommon aggressive subtype of endocervical adenocarcinoma (EAC).Methods and ResultsWe recruited 59 ISMC for clinicopathological analysis, immunohistochemistry (n = 56), and targeted next‐generation sequencing (n = 17). Our cases contained 29 pure and 30 mixed‐type ISMC. Five patients developed local recurrence at 6–32 months (median: 13 months), and died of disease at 16–55 months (median: 16 months). Pure and mixed‐type ISMC showed no significant difference in overall survival and tumour relapse (P > 0.05) except larger tumour size in the pure‐type (P = 0.009). Compared to the usual‐type EAC (n = 217), ISMsC were more frequently associated with large tumour size (P = 0.003), advanced FIGO stage (P = 0.017), lymph node metastasis (P = 0.022), Silva pattern C (P < 0.001), and poor overall survival and short tumour recurrence. SOX2 expression was observed in 82.1% (46/56) ISMC, substantially higher than p63 expression (P < 0.001), while positive SOX17 was present in 3.6% (2/56) cases. PD‐L1 was positive in 41/56 ISMC (73.21%) (combined positive score: range: 1–92, median: 22). Three ISMC patients (17.65%) had PIK3CA mutations, while one each (5.88%) patient harboured an ERBB2, TP53, STK11, and PTEN mutation, respectively.ConclusionWe conclude that ISMC is clinically more aggressive than the usual‐type EAC. ISMC may originate from cervical reserve cells with bidirectional differentiation. PD‐L1 overexpression and the molecular profiles raise the possibility that a subset of ISMC patients may benefit from anti‐PD‐L1 immunotherapy and other targeted therapy, such as mTOR inhibitor and T‐DM1.

Funder

Natural Science Foundation of Zhejiang Province

Publisher

Wiley

Subject

General Medicine,Histology,Pathology and Forensic Medicine

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