Loss of protein expression of hMLH1 and hMSH2 with double primary carcinomas of the stomach and colorectum

Abstract

Abstract. The frequency of synchronous or metachronous multiple primary carcinomas in patients with gastrointestinal carcinoma or colorectal carcinoma (CRC) has been reported to be ~10%. We determined the role of hMSH2 and hMLH1 in double carcinomas with both GC and CRC. Fifty-six patients with synchronous or metachronous colorectal carcinoma with gastric carcinoma (CRC with GC), and 69 patients with CRC alone was included in our study. We investigated their clinicopathological characteristics, family history and immunohistochemical stains of hMSH2 and hMLH1 were compared between the patients with CRC alone and those with both CRC with GC. The defective protein expression of hMSH1 and/or hMLH1 in colorectal carcinomas was significantly higher in patients with both CRC with GC than in those with CRC alone (p<0.0001). The survival rate in patients with both CRC with GC was significantly lower than that in those with CRC alone (p<0.01), in addition, the survival rate in patients with defective protein expression of hMSH2 and/or hMLH1 was higher than in those with a positive protein expression of hMSH2 and/or hMLH1 in CRC with GC (p<0.05). The incidence of defective protein expression of hMSH2 and/or hMLH1 in CRC with GC patients suggests that abnormalities in the function of hMSH2 and hMLH1 may play an important role in carcinogenesis. Our findings indicate that the CRC patients who demonstrate a defective protein expression of hMSH2 and/or hMLH1 have a higher risk of developing secondary carcinoma in the gastrointestinal tract.

Immunophenotypic Evaluation of DNA Mismatch Repair Markers in 2 Cases of Synchronous Histomorphologically Distinct Gastric Adenocarcinomas With Gastrointestinal Stromal Tumors of the Proximal Small Bowel

“…[11][12][13][14][15][16] The combined phenotypic findings of our patients were in line to these earlier reports, as the female patient carrying a free of invasion or metastasis GADC of the intestinal type survives free of disease, whereas the male one carrying an invasive and metastatic GADC of the diffuse type died. Compared with GADCs, the common GIST component carrying intermediate phenotypic combination is likely to have only minor, if any, contribution to the postoperative survival of these 2 cases.…”

The postoperative recurrence and the occurrence of second primary carcinomas in patients with early gastric carcinoma

“…Genetic instability, microsatellite instability, and environmental factors (diet or tobacco use, etc.) have been suggested to be risk factors for the development of multiple primary cancers or second primary cancers in patients with early gastric cancer [24][25][26][27][28].…”

Outcome and Status of Microsatellite Stability in Japanese Atomic Bomb Survivors with Early Gastric Carcinoma

“…For the negative controls, the Dako antibody diluent was replaced by background reducing components without the primary antibodies for each immunostain. 7 Immunohistochemical analyses for hMSH2 and hMLH1 expression were performed with the stomach mucosa specimens of patients who underwent gastrectomy for benign disease. Normal mucosa was used as a positive control.…”

“…We have reported the relationship between double primary cancers (stomach and colorectum) and defective hMSH2 and/or hMLH1 expression. 7 This study aimed to review the results of surgical treatment for early gastric cancer in 117 atomic bomb survivors and 394 control patients, and to compare the clinicopathological characteristics and immunohistochemical staining of hMSH2 and hMLH1 expression between these two groups.…”

“…We have reported the relationship between double primary cancers (stomach and colorectum) and defective hMSH2 and/or hMLH1 expression. 7 This study aimed to review the results of surgical treatment for early gastric cancer in 117 atomic bomb…”