224ASSESSMENT OF MEDULLARY THYROID CARCINOMA WITH THE HELP GRADING SYSTEM AND KI-67 IMMUNOPROLIFERATIVE SCOREMedullary thyroid carcinoma [MTC] derives from the parafollicular C cells, being sporadic in 75% of cases and familial in 25%, due to RET proto-oncogene germinal mutations. This study aimed to evaluate the prognostic impact of molecular and immunohistochemical markers in sporadic MTC. We studied 60 patients with sporadic MTC. For each case, we sought RET somatic mutations in primary cancer and lymph node metastases. Primary cancer also underwent immunohistochemical examination for Ki-67somatic RET mutation was found in 38% of patients, being M918T in 52% of them. We observed a statistically significant association between RET mutations and male gender [P<0.01], tumour size [P<0.05], lymph nodes [P<0.05] and distant metastases [P<0.001], advanced stage [P<0.05], increased risk of persistent disease [P=0.01], and low overall survival [P<0.01]. High Ki-67 levels were similarly associated with extra-thyroid spread [P<0.05], lymph nodes [P<0.05] and distant metastases [P<0.001], advanced stage [P=0.01], and low overall survival [P=0.01]. Combining somatic RET analysis with Ki-67 assessment seems to be useful for increasing the specificity of Ki-67 assessment alone and identifying patients with more aggressive cancer. In our series, only the patients who died during the follow-up had both a somatic RET mutation and a Ki-67 expression level >50?cells/mm2. The grading system remained prognostic when controlled for other factors associated with survival, including age and Known MEN2 syndrome. We conclude that this proposed grading system, which uses only a combination of proliferative activity [Ki-67Index, mitotic count] and coagulative necrosis, is a strong predictor of overall survival in MTC. For counselling, post-resection surveillance, and therapy, they recommended a grading system based on tumour necrosis and mitotic activity to stratify MTC patients betterDr.B.Nagaraja@gmail.comResearch822018Medullary Thyroid Carcinoma,Immunohistochemical,Tumour necrosis, Lymph node metastasesDr.Suvarchala SB,Dr.B.NagarajaAssociate Professor, Department of Pathology, RVS Medical College, RVS Nagar, Tirupathi Road, Andhra Pradesh 517127, India,Associate Professor, Department of Pathology, Government medical College, Kadapa, Puttampalli, Andhra Pradesh 516002, India.