Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers

Yusuke Kobayashi, Kanako Nakamura, Hiroyuki Nomura, Kouji Banno, Haruko Irie, Masataka Adachi, Miho Iida, Kiyoko Umene, Yuya Nogami, Kenta Masuda, Iori Kisu, Arisa Ueki, Wataru Yamagami, Fumio Kataoka, Akira Hirasawa, Eiichiro Tominaga, Nobuyuki Susumu, Daisuke Aoki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective: Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. Methods: Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. Results: Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis,which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. Conclusions: These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalInternational Journal of Gynecological Cancer
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 10 2015
Externally publishedYes

Fingerprint

DNA Mismatch Repair
Endometrial Neoplasms
Ovarian Neoplasms
Immunohistochemistry
Neoplasms
Proteins
Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Germ-Line Mutation
Clinical Medicine
Endometriosis
Endometrium
Ovary
Histology
Guidelines
Neoplasm Metastasis

Keywords

  • Bethesda guideline
  • Dna mismatch repair proteins
  • Lynch syndrome
  • Synchronous primary endometrial and ovarian cancers

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

Cite this

Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers. / Kobayashi, Yusuke; Nakamura, Kanako; Nomura, Hiroyuki; Banno, Kouji; Irie, Haruko; Adachi, Masataka; Iida, Miho; Umene, Kiyoko; Nogami, Yuya; Masuda, Kenta; Kisu, Iori; Ueki, Arisa; Yamagami, Wataru; Kataoka, Fumio; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke.

In: International Journal of Gynecological Cancer, Vol. 25, No. 3, 10.03.2015, p. 440-446.

Research output: Contribution to journalArticle

Kobayashi, Y, Nakamura, K, Nomura, H, Banno, K, Irie, H, Adachi, M, Iida, M, Umene, K, Nogami, Y, Masuda, K, Kisu, I, Ueki, A, Yamagami, W, Kataoka, F, Hirasawa, A, Tominaga, E, Susumu, N & Aoki, D 2015, 'Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers', International Journal of Gynecological Cancer, vol. 25, no. 3, pp. 440-446. https://doi.org/10.1097/IGC.0000000000000377
Kobayashi, Yusuke ; Nakamura, Kanako ; Nomura, Hiroyuki ; Banno, Kouji ; Irie, Haruko ; Adachi, Masataka ; Iida, Miho ; Umene, Kiyoko ; Nogami, Yuya ; Masuda, Kenta ; Kisu, Iori ; Ueki, Arisa ; Yamagami, Wataru ; Kataoka, Fumio ; Hirasawa, Akira ; Tominaga, Eiichiro ; Susumu, Nobuyuki ; Aoki, Daisuke. / Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers. In: International Journal of Gynecological Cancer. 2015 ; Vol. 25, No. 3. pp. 440-446.
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T1 - Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers

AU - Kobayashi, Yusuke

AU - Nakamura, Kanako

AU - Nomura, Hiroyuki

AU - Banno, Kouji

AU - Irie, Haruko

AU - Adachi, Masataka

AU - Iida, Miho

AU - Umene, Kiyoko

AU - Nogami, Yuya

AU - Masuda, Kenta

AU - Kisu, Iori

AU - Ueki, Arisa

AU - Yamagami, Wataru

AU - Kataoka, Fumio

AU - Hirasawa, Akira

AU - Tominaga, Eiichiro

AU - Susumu, Nobuyuki

AU - Aoki, Daisuke

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N2 - Objective: Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. Methods: Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. Results: Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis,which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. Conclusions: These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

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