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Clinicopathologic and Molecular Characteristics of Synchronous Colorectal Carcinoma With Mismatch Repair Deficiency

Nakano, Kayoko, MD*,†; Yamamoto, Hidetaka, MD, PhD*; Fujiwara, Minako, MD, PhD*; Koga, Yutaka, MD, PhD*; Tsuruta, Shinichi, MD*,†; Ihara, Eikichi, MD, PhD; Oki, Eiji, MD, PhD; Nakamura, Masafumi, MD, PhD§; Ogawa, Yoshihiro, MD, PhD; Oda, Yoshinao, MD, PhD*

The American Journal of Surgical Pathology: February 2018 - Volume 42 - Issue 2 - p 172–182
doi: 10.1097/PAS.0000000000000947
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Synchronous colorectal carcinoma (CRC) is a unique disease associated with a high prevalence (∼35%) of microsatellite instability and occasionally with Lynch syndrome. The clinicopathologic and molecular features of synchronous CRC are poorly understood, particularly in Japanese patients. We examined 118 Japanese patients (236 tumors) with synchronous CRC and 117 Japanese patients (117 tumors) with solitary CRC with immunohistochemical staining for TP53 and mismatch repair (MMR) protein (MLH1, MSH2, PMS2, and MSH6) and mutation analyses of KRAS and BRAF genes. The results revealed no significant differences in clinicopathologic, histologic, and molecular findings between the synchronous and solitary CRC groups. Among the 118 synchronous CRC patients, 15 (12.7%) showed loss of MMR protein(s) expression in at least 1 tumor, whereas 103 (87.3%) showed intact expression of all 4 MMR proteins in both tumors. Of note, all patients with MMR deficiency had excellent prognoses. The 15 patients were further subdivided into 2 groups: the Concordant group, with concordant MMR loss (n=9, 7.6%) and the Discordant group, with discordant MMR loss (n=6, 5.1%). The Concordant patients showed concurrent MLH1/PMS2 loss (n=3), concurrent MSH2/MSH6 loss (n=4) and isolated MSH6 loss (n=2) in both tumors, whereas the Discordant patients showed concurrent MLH1/PMS2 loss (n=2), isolated PMS2 loss (n=2) and isolated MSH6 loss (n=2) in a single tumor. On the basis of the MMR expression pattern and BRAF mutation, the Concordant and Discordant groups were suspected to include Lynch syndrome, Lynch-like syndrome and sporadic MLH1 promoter hypermethylated CRC. In addition, KRAS mutation was present in only 1 tumor in a single patient in each group. In conclusion, the frequency of MMR protein deficiency in synchronous CRC in the Japanese population may be lower compared with the reported data from Western populations. MMR protein loss and KRAS and BRAF mutations in synchronous CRCs were heterogenous even in an individual patient.

Departments of *Anatomic Pathology

Medicine and Bioregulatory Science

Surgery and Science

§Surgery and Oncology, Graduate of School of Medical Sciences, Kyushu University, Fukuoka, Japan

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Yoshinao Oda, MD, PhD, Department of Anatomic Pathology, Graduate of School of Medical Science, Kyushu University, Maidashi3-1-1, Higashi-ku, Fukuoka 812-8582, Japan (e-mail: oda@surgpath.med.kyushu-u.ac.jp).

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