RGD Reference Report - Mullerian inhibiting substance type II receptor (MISIIR): a novel, tissue-specific target expressed by gynecologic cancers. - Rat Genome Database

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Mullerian inhibiting substance type II receptor (MISIIR): a novel, tissue-specific target expressed by gynecologic cancers.

Authors: Bakkum-Gamez, JN  Aletti, G  Lewis, KA  Keeney, GL  Thomas, BM  Navarro-Teulon, I  Cliby, WA 
Citation: Bakkum-Gamez JN, etal., Gynecol Oncol. 2008 Jan;108(1):141-8. Epub 2007 Nov 7.
RGD ID: 2315651
Pubmed: PMID:17988723   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ygyno.2007.09.010   (Journal Full-text)

OBJECTIVE: Mullerian inhibiting substance type II receptor (MISIIR) is expressed by ovarian, breast, and prostate cancers [Masiakos PT, et al. Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) Type II Receptor, bind, and are responsive to MIS. Clin Cancer Res 1999;5:3488-99; Hoshiya Y, et al. Mullerian inhibiting substance promotes interferon {gamma}-induced gene expression and apoptosis in breast cancer cells. J Biol Chem 2003;278:51703-12; Hoshiya Y, et al. Mullerian inhibiting substance induces NFkB signaling in breast and prostate cancer cells. Mol. Cell. Endocrinol. 2003;211:43-9. [1-3]]. We investigated the expression patterns of MISIIR in benign and malignant gynecologic tissues and benign non-gynecologic tissues to better assess the relevance of MISIIR as a target for new therapeutic and diagnostic approaches to gynecologic cancers. Secondarily, we examined the impact of MISIIR expression on overall survival (OS) and disease-free survival (DFS) in a cohort of epithelial ovarian cancers (EOC). METHODS: Reverse-transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry (IHC) were used to determine MISIIR expression. EOC cell lines (10), primary EOCs (12), and tissue microarrays (TMAs) containing benign gynecologic (179) and non-gynecologic tissues (25), EOC (182), endometrial carcinomas (109), uterine sarcomas (98), and ovarian dysgerminomas (22) were examined for MISIIR expression. Clinical data were collected for a cohort of 182 EOCs. RESULTS: Ninety-two percent of primary EOCs and 44% of EOC cell lines expressed MISIIR mRNA. We observed moderate or strong MISIIR expression via IHC in the majority of gynecologic cancers: EOC 69% (125/182), ovarian dysgerminomas 77% (17/22), endometrial cancers 75% (82/109), uterine malignant mixed Mullerian tumors (MMMT) 59% (30/51), uterine leiomyosarcomas (LMS) 52% (15/29), and endometrial stromal sarcomas (ESS) 22% (4/18). Over 74% of normal non-gynecologic tissues did not express MISIIR. There was a significant correlation between MISIIR expression and improved OS (p=0.025, Chi square). CONCLUSIONS: In the largest study to date, we report that MISIIR is highly expressed by a wide variety of gynecologic cancers, including cancers currently without effective systemic therapies. Low levels of expression in select non-gynecologic tissues coupled with high expression in gynecologic malignancies make MISIIR an attractive target for novel therapeutics and tumor-directed imaging in the management of gynecologic cancers. Further investigation into the impact of MISIIR expression and OS is also warranted.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dysgerminoma  IEP 2315651protein:increased expression:ovaryRGD 
dysgerminoma  ISOAMHR2 (Homo sapiens)2315651; 2315651protein:increased expression:ovaryRGD 
Endometrial Neoplasms  IEP 2315651protein:increased expression:endometriumRGD 
Endometrial Neoplasms  ISOAMHR2 (Homo sapiens)2315651; 2315651protein:increased expression:endometriumRGD 
leiomyosarcoma  IEP 2315651protein:increased expression:myometriumRGD 
leiomyosarcoma  ISOAMHR2 (Homo sapiens)2315651; 2315651protein:increased expression:myometriumRGD 

Objects Annotated

Genes (Rattus norvegicus)
Amhr2  (anti-Mullerian hormone receptor type 2)

Genes (Mus musculus)
Amhr2  (anti-Mullerian hormone type 2 receptor)

Genes (Homo sapiens)
AMHR2  (anti-Mullerian hormone receptor type 2)


Additional Information