Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors

Abstract

Abstract. Defects in the function of mismatch repair (MMR) genes result in genetic instability, a common feature of malignant progression. This study was conducted to determine the frequency of genetic instability [defined as microsatellite instability (MSI)] and to evaluate the sensitivity/specificity of immunohistochemistry in predicting the deficiency in MMR genes in renal cortical tumors. A total of 51 surgically-resected renal tumors (27 clear cell, 10 papillary, 5 chromophobe carcinomas and 9 oncocytomas) were studied. We also analyzed the correlation with clinicopathological parameters, the MSI status (assessed by using 5 microsatellite markers: D2S123, D11S904, D3S1621, D3S1683 and BAT26), and the immunohistochemical expression of 2 major MMR genes [the human mutL homolog 1 (hMLH1) and the human mutS homolog 2 (hMSH2)]. Sixteen cases (31.4%) showed MSI: Three (5.9%) demonstrated a high level of MSI, 11 (21.6%) demonstrated a low level of MSI, 2 (3.9%) presented with a loss of heterozygosity, and the remaining 35 (68.6%) exhibited microsatellite stability. The loss of hMLH1 and hMSH2 immunohistochemical expressions was observed in 5/51 (9.8%) and 9/51 (17.6%) cases, respectively. The complete absence of both hMLH1 and hMSH2 immunohistochemical expressions was observed only in the 3 cases with a high level of MSI. This study showed that defects in MMR genes are involved in renal carcinogenesis and correlate with the occurrence of MSI.

Ectopic Expression of Human MutS Homologue 2 on Renal Carcinoma Cells Is Induced by Oxidative Stress with Interleukin-18 Promotion via p38 Mitogen-activated Protein Kinase (MAPK) and c-Jun N-terminal Kinase (JNK) Signaling Pathways

“…The hMSH2 mutations have a higher incidence of extracolonic tumors (6). The defects of both MMR genes are involved in renal carcinogenesis and correlate with the occurrence of microsatellite instability (7).…”

Clinical Pan-Cancer Assessment of Mismatch Repair Deficiency Using Tumor-Only, Targeted Next-Generation Sequencing

“…We measured MMR-D frequencies detected using the OncoPanel algorithm in 20,301 samples across tumor types (Tables 1 and 2 ) and compared them to historical reports of MMR-D prevalence (Tables 1 and 3 , Fig 1 ). 18 - 39 The OncoPanel cohort comprised 13,542 primary biopsies, 4,734 metastatic recurrences, 655 local recurrences, and 1,370 tumors with unspecified biopsy site.…”

“… Comparison of mismatch repair–deficient (MMR-D)/microsatellite instability–high (MSI-H) patterns across tumor types. Across all studies described in Table 3 , 18 - 39 the frequency of MMR-D or MSI-H was reported across all six cohorts in nine tumor types: colorectal, endometrial, esophagogastric, head and neck, hepatocellular, prostate, renal cell carcinoma, thyroid cancer, and soft tissue sarcoma. Hepatocellular carcinoma and thyroid cancer had considerably higher MSI-H rates reported in the review by Dudley et al 19 …”

Complete Remission of Liver and Bone Metastases After Nivolumab Treatment in a Patient with Renal Cell Carcinoma: The Potential Implication of MLH1 Mutations

“…A deficiency in the cell's ability to repair errors in the DNA sequence that occur during cell division leads to changes in mircosatellite repeats, causing microsatellite instability [7][8][9]. The DNA mismatch repair (MMR) system is a biological pathway essential for maintenance of genomic stability and reduction of microsatellite instability [7].…”