Anti Mullerian Hormone (Amh) - A Sensitive Marker To Assess Ovarian Cancer

According to a research report published in the A year 2014, by scientists of Tata Memorial Hospital, Mumbai, India; ovarian Cancer is the fifth leading cause of total cancer related deaths. The survival rate is only about 5 years in 30-40% of the patients. According to experts, the most common cause is related to delayed diagnosis. Although there are many advanced diagnostic tools that involve biochemical tests, diagnosis using imaging techniques, etc.; detection and diagnosing in the initial symptomatic phase is still a major road block. A sensitive biomarker that is expressed even in early stages is a need and ray of hope for reducing the burden of mortality on ovarian cancer.

Ovaries are the primary organs in a female reproductive system responsible for production of female gametes i.e. oocytes and steroidal sex hormones such as progesterone, testosterone and Estrogen. The ova produced in the ovary travels through the fallopian tube to the uterus, where it is fertilised with the male gametes or sperms, if present.

This fertilisation results in formation of fetus, medically terming a woman pregnant. This complex structured organ has variable and important functions that relates to Infertility and reproductive mechanisms in females and hence, its health is imperative in all females. Disorders of ovary such as polycystic ovarian disease (PCOD), ovarian cancer, premature ovarian failure, ovarian torsion, ovarian cysts, etc. have been recorded in major. Among these conditions, ovarian cancer, its diagnosis and treatment remains the biggest challenge world over.

Ovarian Cancer Overview
Ovarian cancer though is a disease affecting a single organ, it is a broad umbrella term which includes multiple types depending on the origin and category of tumour. ovarian cancer involves a group of three different tumour types viz. epithelial tumour, germline tumour and sex cord stromal tumours. Highest percentage of ovarian cancer malignancy is contributed by those of epithelial origin. Around 82% of ovarian cancers are of epithelial origin and the predominant cell types are serus, endometrioid and mucinous, Malignant germ cell tumours, contribute approximately to 5% of ovarian malignancies. The major tumour types from germ cell origin include endodermal sinus tumour, choriocarcinoma, malignant teratomas, dysger-minoma, etc. Sex cord stromal tumours represent about 10% of ovarian cancer load and they originate from the mesenchymal stem cells in the ovarian cortex. The major tumour types of sex cord stromal neoplasms include granulosa theca cell tumours, granulosa cell tumours (GCTS) and sertoli cell tumours. The poor symptoms associated with ovarian cancer makes the early diagnosis difficult. Delayed diagnosis and treatment is often associated with poor response to therapies and neoplastic conditions. Hence, discovery of a biomarker that can predict early diagnosis is a need of the hour to minimise the load of mortality due to ovarian cancer

What is Mullerian duct?
Mullerian duct is a paired duct present in the embryo and is responsible for differential sex organ formation. In females, it becomes either a fallopian tube, vagina, uterus or in case of males can become testes or its other counter parts.

Anti-Mullerian hormones (AMH)
This is a peptide hormone that belongs to the Transforming growth factor-beta (TGF-beta) growth factor family of peptides. Its measurable levels can be found in the blood of both females and males, In males, AMH is synthesised by the sertoli cells of testes in fetus from the 5 week of embryonal development and continues throughout life. Its unique effect in males include inhibition of mullerian duct development to prevent embryo development with male phenotypic characters or in simple terms prevents development of female reproductive organs in a male fetus. In females, it is synthesised by the ovarian cells from the 36 gestational week through the granulosa cells and is required for folliculogenesis. Yet, the complete role of AMH in adult females is poorly understood. However, recent studies have highlighted Anti-Mullerian hormone as a diagnostic marker for ovarian cancer. At present AMH is proved to be a robust circulation marker for granulosa cell tumour. Apart from its role as a diagnostic marker, AMH is also believed to be a potential therapeutic agent. Since Anti-Mullerian hormone has an inhibitory role in mullerian ducts, it is believed to inhibit epithelial ovarian cancer.

Biomarkers for ovarian cancer and Anti-Mullerian hormone
Although ovarian cancer occurs in variable forms based on tumour type, they vary greatly from each other from histological point of view, in tumour behaviour, in response to anti- cancer therapies, gene expression patterns, etc. Hence, the diagnosis of each type depends upon specific tumour biomarker. Some of the most widely used and commonly known ovarian tumour markers include cancer antigen 125 , Inhibin, CASA, Hla B27, Prostasin, hCGbef, Interleukin-6, etc.

Research is still underway for discovering a highly efficient and sensitive ovarian tumour marker. From last one decade, studies are being conducted on AMH for identifying its potential as an ideal tumour marker: Serum Anti-Mullerian hormone levels are found to be a good marker for malignancies originating from granulosa cells and hence have emerged as a granulosa cell tumour (GCT) marker: 76-93% of patients who are affected by granulosa cell tumours are found to have elevated levels of AMH. Anti-Mullerian hormone levels along with inhibin acts as a early marker for detection of Cancer originating from tumours of granulosa cells. Anti-Mullerian hormone is found to be a more sensitive marker as compared to inhibin.

Significance of Anti-Mullerian hormone

Serum AMH levels are considered to be a highly sensitive biomarker as they are detectable even in the early stages.
Anti-Mullerian hormone has advantages over other ovarian tumour markers such as Estrogen and inhibin in regards to sensitivity.
AMH may also be applicable as a chemotherapeutic agent for epithelial ovarian cancer.
Detection of Anti-Mullerian hormone level serves as an additional marker for detection and identification of PCOD.
With increasing age there is a decrease in the number of follicles in ovary and also the levels of AMH. Hence, Anti-Mullerian hormone can serve as an early marker for determination of ovarian function.
AMH is an important marker for male hypogonadism. Lower levels of Anti-Mullerian hormone is an excellent marker for congenital hypogonadism.
AMH measurements can also be used to assess treatment prognosis during follow-up of patients undergoing therapy for improving gonadal functions.
Recent research findings suggest that Anti-Mullerian hormone plays and important role in detection of other neoplastic conditions such as prostate cancer.
Anti-Mullerian Hormone is one of the most important and emerging diagnostic marker that can be detected even in early stages of ovarian cancer and research is under pipeline to exploit it further even as a therapeutic tool. Thyrocare provides sensitive testing option for AMH using ELISA technology.