Developing a deeper insight into reproductive biomarkers

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Abstract

The development of biomarkers of reproductive medicine is still in its infancy because many black boxes are still present in reproductive medicine. Novel approaches to human infertility diagnostics and treatment must be developed because reproductive medicine has lagged behind in the implementation of biomarkers in clinical medicine. Despite the dearth of the available literature, the current rapid pace of publications suggests that this gap will soon be filled therefore; this review is a précis of the research that has been done so far and will provide a basis for the development of biomarkers in reproductive medicine.

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Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Weiva Sieh, Martin Köbel, Teri Longacre … (2013)

Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. Carraresi Foundation and others. Copyright © 2013 Elsevier Ltd. All rights reserved.

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Seminal plasma as a diagnostic fluid for male reproductive system disorders.

Andrei P. Drabovich, Punit Saraon, Keith Jarvi … (2014)

Molecular biomarkers hold promise to advance the noninvasive diagnosis of male reproductive system disorders and facilitate the identification and management of these conditions through screening, early diagnosis and more accurate prognosis. Seminal plasma has great potential as a proximal fluid for protein biomarker discovery and as a clinical sample for noninvasive diagnostics. The seminal plasma proteome contains thousands of proteins and includes a large number of tissue-specific proteins that might accurately indicate a pathological process in the tissue of origin. Potential protein biomarkers for male reproductive system disorders are more abundant in seminal plasma than in blood serum or urine, and, therefore, are more easily identified and quantified in semen by mass spectrometry and other techniques. These methods have enabled elaboration of the composition of the seminal plasma proteome and the tissue specificity of seminal plasma proteins. Strategies have been developed to discover protein biomarkers in seminal plasma through integrated 'omics' approaches. Biomarkers of male infertility and prostate cancer are now emerging, and it is evident that seminal plasma has the potential to complement other diagnostic tools available in urology clinics.

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Precursor lesions of ovarian epithelial malignancy.

Darren M. Wells, K Feeley (2001)

Most ovarian carcinomas arise from the mesothelial surface lining of the ovaries, or from invaginations of this lining into the superficial ovarian cortex to form cortical inclusion cysts. The native ovarian surface mesothelium is of an 'uncommitted' phenotype, and has potential to modulate to epithelial or mesenchymal phenotypes in response to signals such as those associated with ovulation. The exposure of the mesothelial lining of an inclusion cyst to the ovarian stromal microenvironment may be responsible for the phenotypic change to Müllerian epithelium so commonly seen in these cysts. Müllerian metaplasia is usually to a serous phenotype, and it is possible that undefined molecular events occurring in an inclusion cyst that has undergone Müllerian metaplasia may initiate neoplastic change in these cysts. This may be the developmental pathway of most invasive serous carcinomas. Occasional rare cases of ovarian intraepithelial neoplasia, manifested by epithelial atypia in an inclusion cyst or on the surface epithelium without invasive carcinoma, are identified histologically. Serous borderline tumours represent a separate category and in most cases probably do not progress to frank carcinoma. Mucinous carcinomas may in some cases have arisen from pre-existing benign and borderline mucinous tumours. Endometriosis of the ovary is associated with genetic abnormalities and is frequently found in association with clear cell and endometrioid carcinomas, suggesting that in many cases these latter two types of carcinoma may have arisen directly from endometriotic deposits. Ovaries removed prophylactically from women with a family history of ovarian carcinoma or with a mutation in one of the genes predisposing to ovarian carcinoma should be processed in their entirety, and examined closely not just for obviously neoplastic lesions, but also for more subtle morphological abnormalities of the surface epithelium or the epithelium lining cortical inclusion cysts.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Exp Reprod Med

Journal ID (iso-abbrev): Clin Exp Reprod Med

Journal ID (publisher-id): CERM

Title: Clinical and Experimental Reproductive Medicine

Publisher: The Korean Society for Reproductive Medicine

ISSN (Print): 2233-8233

ISSN (Electronic): 2233-8241

Publication date (Print): December 2017

Publication date (Electronic): 31 December 2017

Volume: 44

Issue: 4

Pages: 159-170

Affiliations

[1 ]Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan.

[2 ]Genome Centre for Molecular Based Diagnosis and Research, Lahore, Pakistan.

[3 ]Lahore College for Women University, Lahore, Pakistan.

Author notes

Corresponding author: Hamid Bashir. Centre for Applied Molecular Biology, University of the Punjab, 87-West Canal Bank Road, Lahore-53700, Pakistan. Tel: +92-42-5293141, Fax: +92-42-5293149, hamid.camb@ 123456pu.edu.pk

Article

DOI: 10.5653/cerm.2017.44.4.159

PMC ID: 5783911

PubMed ID: 29376011

SO-VID: 4db2aec5-e4b2-4a58-a5ed-2f68dbd56719

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 01 March 2017

Date revision received : 26 October 2017

Date accepted : 20 November 2017

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Developing a deeper insight into reproductive biomarkers

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Bioscientifica Reproduction

Most cited references 117

Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

Seminal plasma as a diagnostic fluid for male reproductive system disorders.

Precursor lesions of ovarian epithelial malignancy.

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