Gene Mutations of K-Rasin Gallbladder Mucosae and... : Official journal of the American College of Gastroenterology | ACG (original) (raw)

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Gene Mutations of K-Ras in Gallbladder Mucosae and Gallbladder Carcinoma With An Anomalous Junction of The Pancreaticobiliary Duct

Hanada, Keiji MD1; Tsuchida, Akira MD1; Iwao, Toshiyasu MD1; Eguchi, Noriaki MD1; Sasaki, Tamito MD1; Morinaka, Kenji MD1; Matsubara, Kenji MD1; Kawasaki, Yosuke MD1; Yamamoto, Shigeru MD1; Kajiyama, Goro MD2

1_Department of Internal Medicine, Onomichi General Hospital Hiroshima, Japan_

2_First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan_

Reprint requests and correspondence: Keiji Hanada, MD, Department of Internal Medicine, Onomichi General Hospital, 7-19 Kohama-cho, Onomichi, Hiroshima, 722-0002, Japan

Received September. 1, 1998; accepted January. 18, 1999

Abstract

OBJECTIVE:

In this study, we examined the mutational spectrum of K-ras in cases of gallbladder and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct (AJPBD).

METHODS:

We examined 35 gallbladders with AJPBD (20 with hyperplasia, 15 with carcinoma) and 38 gallbladders without AJPBD (four normal gallbladders, four with hyperplasia, six with adenoma, 24 with carcinoma). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to detect mutations in codon 12 or 13 of K-ras.

RESULTS:

In the cases with AJPBD, the prevalences of K-ras mutation were 15% (3/20) in hyperplasia, 60% (6/10) in stage I carcinoma, and 100% (5/5) in stage II–IV carcinoma. In the cases without AJPBD, the prevalences of K-ras mutation were 0% (0/4) in normal gallbladder, 0% (0/4) in hyperplasia, 17% (1/6) in adenoma, 7% (1/16) in stage I carcinoma, and 38% (3/8) in stage II–IV carcinoma. Prevalences of K-ras mutation in hyperplasia and carcinoma with AJPBD were greater than those without AJPBD (p < 0.05). The point mutation of GGT to GAT in codon 12 was frequently observed in the cases with AJPBD.

CONCLUSIONS:

These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD.