Clinicopathological and Molecular Differences Between Gastric-type Mucinous Carcinoma and Usual-type Endocervical Adenocarcinoma of the Uterine Cervix

Abstract

Background/Aim: We investigated differences in the clinicopathological and molecular characteristics between gastric-type mucinous carcinoma (GMC) and usualtype endocervical adenocarcinoma (UEA). Patients and Methods: We collected the clinicopathological information and performed targeted genomic sequencing analysis. Results: GMCs exhibited significantly deeper invasion depth, larger horizontal spread, more advanced stage, more frequent distant metastasis, and more frequent parametrial and vaginal extension. Disease-free survival time of GMC patients was significantly shorter than that of UEA patients. GMCs displayed mutant p53 immunostaining pattern, whereas UEAs exhibited p16 block positivity. GMCs harbored mutations in KRAS, TP53, NF1, CDKN2A, STK11, and ARID1A. One GMC exhibited MDM2 amplification. In contrast, UEAs harbored mutations in HRAS, PIK3CA, and BRCA2. Two UEAs were found to have novel TP53 mutations. Conclusion: GMC is associated with more aggressive behavior than UEA. Distinctive p53 and p16 immunostaining patterns enable differential diagnosis. GMC and UEA exhibit genetic heterogeneity with potentially actionable molecular alterations. Cervical cancer is the fourth most common gynecological malignancy and the fourth leading cause of cancer-related death in women worldwide (1, 2), although cervicovaginal cytology screening decreased the incidence rate of cervical cancer and its associated mortality rate. Adenocarcinoma of the uterine cervix is relatively less common than squamous cell carcinoma and accounts for approximately 10-20% of all cervical cancers (3, 4). However, despite the declined incidence of cervical cancer, the proportion of endocervical adenocarcinoma has increased (4-6). The International Endocervical Adenocarcinoma Criteria and Classification (IECC) is a recent system to classify endocervical adenocarcinoma into human papillomavirus (HPV)-associated adenocarcinoma (HPVA) and non-HPV-associated adenocarcinoma (NHPVA) categories based on morphological features (7). Identification of high-risk HPV, notable mitotic activity, and numerous apoptotic bodies across the glandular lumina allowed diagnosing HPVAs. The HPVAs were further divided into usual type, mucinous type (intestinal type, signet ring cell type, and not otherwise specified), villoglandular type, and invasive stratified mucin-producing carcinoma (invasive stratified mucin-producing intraepithelial lesion), depending on their cytoplasmic mucin component and nuclear characteristics. Meanwhile, NHPVAs include gastric-type mucinous carcinoma (GMC), mesonephric carcinoma, serous carcinoma, clear cell carcinoma, and endometrioid adenocarcinoma. Among these carcinomas, GMC, which is the second most common subtype of endocervical adenocarcinoma, is included in the 2014 World Health Organization (WHO) Classification of Tumours of Female Reproductive Organs (1). Although the incidence of 627 This article is freely accessible online.

Targeted Genomic Sequencing Reveals Different Evolutionary Patterns Between Locally and Distally Recurrent Glioblastomas

“…DNA and RNA were quantified using the Qubit 2.0 Fluorometer (Thermo Fisher Scientific). DNA and RNA libraries were prepared as previously described (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). These DNA libraries were generated from 20 ng of DNA per sample using an Ion AmpliSeq Library Kit 2.0 (Thermo Fisher Scientific) and the Oncomine Comprehensive Assay v1 (OCA v1) panel (Thermo Fisher Scientific).…”

“…Analysis of the sequencing data was performed using the Torrent Suite Software v5.2.2 (Thermo Fisher Scientific). This workflow was created by adding a custom hotspot Browser Extensible Data file to report mutations of interest and a custom CNA baseline (described below) using the manufacturer's default workflow, as described previously (24,25,35). The pipeline used included signaling processing, base calling, quality score assignment, adapter trimming, read mapping to the human genome assembly GRCh37, quality control of mapping, coverage analysis with downsampling, and variant calling.…”

“…Gene fusions were detected using the fusion detection module within the Ion Reporter Software (Thermo Fisher Scientific) workflow. This pipeline only reported fusions that were annotated previously, as defined in a reference file preloaded into the workflow (24,25,35).…”

Gastric-type endocervical adenocarcinoma: Review of clinicopathologic characteristics and recent advances

“…Microscopically, gastric-type ECAC is composed of irregularly shaped, small to cystically dilated glands with varying degrees of architectural complexity including intraluminal papillae and occasionally cribriform and solid growth (Figure 2) [5,6,10]. A desmoplastic stromal reaction may be present around the glands at the deep invasive edge of the tumor [5].…”

Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation

“…Immunostaining was performed using a compact polymer method (Bond Polymer Refine Detection kit, Leica Biosystems, Newcastle, United Kingdom) [ 13 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. The tumor cells showed focal nuclear PAX2 immunoreactivity with mild-to-moderate staining intensity ( Figure 2 A).…”