Patients negative for the biomarker can be spared of neck dissection, say Dr. Amit Dutt (seated left) and Dr. Sudhir Nair (seated right).

Only those patients who have higher levels of the biomarker are likely to have cancer spread to the lymph nodes. So the biomarker will help doctors to decide which patients could be spared of complex surgeries to remove the lymph nodes.

Researchers at the Tata Memorial Centre in Mumbai have identified a biomarker that will help doctors decide whether patients with early-stage tongue cancer should undergo neck dissection (surgery) to remove 20-30 lymph nodes. Patients negative for the biomarker can be spared of neck surgery. Studies were carried out on 57 patients.

In nearly 70% of patients with early-stage tongue cancer, the tumour would not have spread to the lymph nodes.  These patients therefore need not have to undergo neck dissection to remove the lymph nodes to prevent disease recurrence. But in the absence of a reliable biomarker capable of pointing out in which patients the disease will recur, doctors routinely remove the affected part of the tongue and the lymph nodes in all patients who present with early-stage tongue cancer.

Nearly 80% survive and are disease-free if tongue cancer is detected early. But once cancer spreads to the lymph nodes, the survival rate reduces to 40%. “Currently, surgical removal of the lymph nodes and studying them is the only way of knowing if the cancer has spread. In early-stage tongue cancer patients, the cancer in the lymph nodes cannot be accurately diagnosed through clinical examination or a scan,” says Dr. Sudhir Nair from the Division of Head and Neck Oncology at the Tata Memorial Centre and one of the authors of the paper.

“The discovery of the biomarker — MMP10 protein —  potentially fills this gap. Only those patients who have higher levels of this protein [overexpressed] are likely to have cancer spread to the lymph nodes. So the biomarker will help doctors to decide which patients could be spared of complex surgeries to remove the lymph nodes,” says Dr. Amit Dutt from the Integrated Genomics Laboratory, ACTREC at the Tata Memorial Centre and who led the research team. The results were published in the journal Oral Oncology. Dr. Dutt is an Intermediate Fellow of the Wellcome Trust DBT India Alliance and this paper was part of the fellowship work.

The biomarker can be identified using a simple and routine immuno histochemical analysis using widely available facility at pathology centres.

The researchers validated their findings using data of 253 patients from the Cancer Genome Atlas and other studies. “The MMP10 biomarker was significantly higher in four of the five data sets,” Dr. Dutt says. “We will be further validating out finding using 500-odd samples collected by our hospital during an earlier trial.”

Chewing tobacco signature

The 57 patients studied were negative for human papillomavirus (HPV) but were habitual users of chewing tobacco. Although chewing tobacco has been associated with oral cancer, there has been no direct evidence linking the two at the genome level. This study has for the first time shown a direct link between chewing tobacco and tongue cancer.

Those chewing tobacco had a classic signature in the genome in the form of a specific type of mutation (transversion mutation). “In our study, 53% of all patients have this tobacco signature. This mutation is driven by tobacco usage,” says Dr. Dutt.

A set of mutations called hallmark mutations are generally seen in tongue cancer patients. All the patients who showed the unique mutation caused by chewing tobacco also had the hallmark mutations. “This suggests that the progression of the disease follows a similar path as in the case of Caucasians,” Dr. Pawan Upadhyay, the first author of the study. In Caucasians, tobacco smoking and HPV are the main causal factors of tongue cancer as chewing tobacco usage is not common.

Published in The Hindu on August 23, 2017