Endometrial cancer (EC) is a common malignant tumor in women, originating from the endometrial epithelium. Molecular classification of EC aids in guiding treatment, assessing prognosis, and screening for Lynch syndrome. Detection of mismatch repair (MMR) deficiency and microsatellite instability (MSI) status is crucial for guiding immunotherapy and Lynch syndrome screening. This study presents a case of poorly differentiated endometrioid carcinoma, which exhibited MMR deficiency but was microsatellite stable (MSS). Despite the MSS status, the tumor showed signs of genomic instability. Further MLH1 methylation testing suggested that MLH1 promoter methylation may have partially suppressed its expression. These results indicate that the immunohistochemistry (IHC) analysis yielded a negative result, whereas the MSI testing suggested that, although methylation of the MLH1 promoter allows MLH1 expression to largely maintain general genomic stability, it still exhibits signs of underlying instability. In conclusion, for endometrial cancer patients exhibiting dMMR by IHC but MSS by MSI testing, MLH1 promoter methylation testing becomes even more critical. This not only aids in screening for Lynch syndrome, enabling pathologists to make a more precise diagnosis, but also provides important guidance for clinical treatment decisions.

Background: Breast cancer has emerged as the foremost cause of female mortality worldwide, with triple negative breast cancer accounting for approximately 10–15% of all breast cancer cases. The triple negative breast cancer family has obvious familial heritability, but no potential pathogenic variation was found in BRCA1/2. Case presentation: The patient was a 56-year-old woman of Han ethnicity. The clinical characteristics of this patient with breast cancer were summarized, peripheral blood of one normal female and two patients with breast cancer in this family was collected, DNA was extracted, and the potential pathogenic variation was analyzed by whole exome sequencing. The normal female and two patients with breast cancer in this family shared a maternal grandmother. The proband’s right breast mass was punctured, and the biopsy showed invasive carcinoma of the right breast, grade II–III, with necrosis. No mutation was found in BRCA1/2 gene test; immunohistochemical of surgical specimens showed triple negative breast cancer. Three mutation types and 17 gene mutation sites were detected through bioinformatics prediction analysis on the basis of co-segregation of genotype and phenotype within the family and whole exome sequencing results. Combined with the Cancer Genome Atlas database comprehensive analysis, the MT1E c.G107A (p.C36Y) mutation may be a potential pathogenic site. Conclusions: Through whole exome sequencing, we identified a total of 17 potential pathogenic mutation loci, none of which have been reported thus far. Therefore, our work expanded the gene mutation spectrum of familial hereditary triple negative breast cancer, which can provide more basis for family genetic counseling.