Ovarian clear cell carcinoma with plasma cell‐rich inflammatory stroma: a clear cell carcinoma subgroup with distinct clinicopathological features

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

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Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma

Diagnostic Pathology ◽

10.1186/s13000-021-01071-w ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Huijuan Ge ◽

Yaoxin Xiao ◽

Guangqi Qin ◽

Yanzi Gu ◽

Xu Cai ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Tumor Infiltrating Lymphocytes ◽

Tissue Microarrays ◽

Ovarian Clear Cell Carcinoma ◽

Repair Deficiency ◽

Ovarian Epithelial Carcinoma ◽

Histological Characteristics ◽

Infiltrating Lymphocytes

Abstract Background Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency. Methods A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays. Results dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %). Conclusions Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.

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250 Differing risk of ovarian clear cell carcinoma in Asian subpopulations

10.1136/ijgc-2020-igcs.215 ◽

2020 ◽

Author(s):

S Chow ◽

D Kapp ◽

C Liao ◽

A Mann ◽

O Dorigo ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Ovarian Clear Cell Carcinoma

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