TY - JOUR
T1 - Heterogeneous distribution of K-ras-mutated epithelia in mucinous ovarian tumors with special reference to histopathology
AU - Mandai, M.
AU - Konishi, I.
AU - Kuroda, H.
AU - Komatsu, T.
AU - Yamamoto, S.
AU - Nanbu, K.
AU - Matsushita, K.
AU - Fukumoto, M.
AU - Yamabe, H.
AU - Mori, T.
N1 - Funding Information:
From the Department of Gynecology and Obstetrics, and Department of Pathology, Faculty of Medicine, Kyoto University; Laboratory of Anatomic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan. Accepted for publication March 31, 1997. Supported by a Grant-in-Aid for Scientific Research (No. 07457608) from the Ministry of Education, Science and Culture, Japan (I.K). Address correspondence and reprints request to Ikuo Konishi, MD, Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan. Copyright © 1998 by W.B. Saunders Company 0046-8177/97/29014)00758.00/0 lions. In another LMP tumor, all of the IMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinons tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the "adenoma-carcinoma sequence" in some mucinous ovarian tumors, but in other cases an alternative pathway may also be possible. HUM PATHOL 28:034--040. Copyright © 1998 by W.B. Saunders Company Key words: K-ras mutation, heterogeneity, mucinous ovarian tumor, adenoma-carcinoma sequence, microdissection.
PY - 1998
Y1 - 1998
N2 - The carcinogenic process of epithelial ovarian carcinomas is still unknown, and both pathways of de novo carcinogenesis from the surface epithelium and malignant transformation of benign cystadenoma have been suggested. Especially in mucinous ovarian tumors, the transition from benign cystadenomas to tumors of low malignant potential (LMP) or carcinomas has been implicated. To elucidate this possibility, we analyzed the presence or absence of heterogeneity of the K-ras mutation corresponding to the histological heterogeneity in 71 epithelial ovarian tumors, including 31 mucinous tumors. K-ras mutation was identified in nine mucinous tumors (4 of 10 carcinomas, 4 0 14 LMP tumors, and 1 of 7 cystadenomas) and in two non- mucinous carcinomas. Microdissection of multiple sites with reference to their histological appearance showed the heterogeneous distribution of K- ras-mutated epithelia in two of the nine mucinous tumors. One mucinous carcinoma showed K-ras mutation in all of the histologically LMP and malignant portions, but not in benign portions. In another IMP tumor, all of the LMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinous tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the 'adenoma- carcinoma sequence' in some mucimous ovarian tumors, but in other cases an alternative pathway may also be possible.
AB - The carcinogenic process of epithelial ovarian carcinomas is still unknown, and both pathways of de novo carcinogenesis from the surface epithelium and malignant transformation of benign cystadenoma have been suggested. Especially in mucinous ovarian tumors, the transition from benign cystadenomas to tumors of low malignant potential (LMP) or carcinomas has been implicated. To elucidate this possibility, we analyzed the presence or absence of heterogeneity of the K-ras mutation corresponding to the histological heterogeneity in 71 epithelial ovarian tumors, including 31 mucinous tumors. K-ras mutation was identified in nine mucinous tumors (4 of 10 carcinomas, 4 0 14 LMP tumors, and 1 of 7 cystadenomas) and in two non- mucinous carcinomas. Microdissection of multiple sites with reference to their histological appearance showed the heterogeneous distribution of K- ras-mutated epithelia in two of the nine mucinous tumors. One mucinous carcinoma showed K-ras mutation in all of the histologically LMP and malignant portions, but not in benign portions. In another IMP tumor, all of the LMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinous tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the 'adenoma- carcinoma sequence' in some mucimous ovarian tumors, but in other cases an alternative pathway may also be possible.
KW - Adenoma-carcinoma sequence
KW - Heterogeneity
KW - K-ras mutation
KW - Microdissection
KW - Mucinous ovarian tumor
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U2 - 10.1016/S0046-8177(98)90387-2
DO - 10.1016/S0046-8177(98)90387-2
M3 - Article
C2 - 9445131
AN - SCOPUS:0031964463
VL - 29
SP - 34
EP - 40
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 1
ER -