Literature DB >> 23365123

DNA mismatch repair protein (MSH6) correlated with the responses of atypical pituitary adenomas and pituitary carcinomas to temozolomide: the national cooperative study by the Japan Society for Hypothalamic and Pituitary Tumors.

Toshio Hirohata1, Kenichiro Asano, Yoshikazu Ogawa, Shingo Takano, Kosaku Amano, Osamu Isozaki, Yoshiyasu Iwai, Kiyohiko Sakata, Noriaki Fukuhara, Hiroshi Nishioka, Shozo Yamada, Shingo Fujio, Kazunori Arita, Koji Takano, Atsushi Tominaga, Naomi Hizuka, Hidetoshi Ikeda, R Yoshiyuki Osamura, Shigeyuki Tahara, Yudo Ishii, Takakazu Kawamata, Akira Shimatsu, Akira Teramoto, Akira Matsuno.   

Abstract

CONTEXT: Temozolomide (TMZ) is an alkylating agent and was a first-line chemotherapeutic agent for malignant gliomas. Recently, TMZ has been documented to be effective against atypical pituitary adenomas (APAs) and pituitary carcinomas (PCs).
OBJECTIVE: The clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively.
DESIGN: Members of the Japan Society of Hypothalamic and Pituitary Tumors were surveyed regarding the clinical characteristics of APAs and PCs treated with TMZ. Stored tumor samples were gathered from the responders and were assessed by the immunohistochemistry of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, p53, MSH6, and anterior pituitary hormones. Responses to TMZ treatment were defined as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 2.0.
SUBJECTS: Three samples from 3 subjects with APA and 11 samples from 10 subjects with PC were available.
RESULTS: The 13 subjects had APAs and PCs consisting of 5 prolactin-producing tumors, 5 ACTH-producing tumors, and 3 null cell adenomas. The clinical response to TMZ treatment was as follows: 4 cases of CR and PR (31%), 2 cases of SD (15%), 6 cases of recurrence after CR and PR (46%), and 1 case of PD (8%). However, considerable subjects had recurrent disease after a response to TMZ. The immunohistochemical findings of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, and p53 did not show any significant correlation with the efficacy of TMZ. However, the immunopositivity of MSH6 was positively correlated with TMZ response (P = .015, Fisher's exact test).
CONCLUSIONS: This study showed that preserving MSH6 function was contributory to the effectiveness of TMZ in malignant pituitary neoplasms. It is necessary to survey more cases and evaluate multifactor analyses.

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Year:  2013        PMID: 23365123     DOI: 10.1210/jc.2012-2924

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


  33 in total

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Review 4.  How effective is temozolomide for treating pituitary tumours and when should it be used?

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Review 5.  Malignant transformation in non-functioning pituitary adenomas (pituitary carcinoma).

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Review 6.  Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide.

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7.  An Institutional Experience of Tumor Progression to Pituitary Carcinoma in a 15-Year Cohort of 1055 Consecutive Pituitary Neuroendocrine Tumors.

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8.  Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

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Review 9.  Immunohistochemical Biomarkers in Pituitary Pathology.

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Review 10.  Management of NFAs: medical treatment.

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