Journal of Clinical and Diagnostic Research. 2019 Jan, Vol-13(1): EC12-EC17 12 12 DOI: 10.7860/JCDR/2019/39685.12497 Original Article Pathology Section CD8+ T Lymphocyte Infiltration: A Favourable Prognostic Indicator in Indian Patients with Breast Carcinoma INTRODUCTION Breast cancer is the most commonly diagnosed cancer in women worldwide with over 2.1 million new cases per year accounting for almost one in four cancer cases among women [1]. There are geographic and ethic variations in the incidence and mortality due to breast cancer. Although, these may be explained by hereditary and genetic factors like family history of breast cancer or inherited mutations, studies of migrants have shown that non-hereditary factors are the major drivers of the observed international and inter- ethnic differences in incidence. The development of a malignancy and its progression is a complex interplay of genetic abnormalities, environmental factors and host interactions of the tumour cells. One such important but still poorly understood non-hereditary factor in the development and prognosis of a tumour is the role of host immune system. Since the initial reports of TILs over 40-years- ago, their role in the pathobiology is still being debated [2,3]. Initial views that high TILs represent anti-tumour immunity and translate to good prognosis were found to be overly simplistic. While TILs represent anti-tumour immune response, the outcome depends on many factors like the presence of antigen presenting cells, immunostimulatory cytokines, the subsets of lymphocytes involved, optimal surface molecule expression by both the tumour cells and the infiltrating lymphocytes etc. The complexities of these interactions are just beginning to be defined and various forms of cancer appear to have different immune system requirements [3]. Previous studies have shown that high TILs at diagnosis are associated with a higher pathological complete response after neoadjuvant chemotherapy [4]. Similarly higher baseline TILs in some randomised controlled trials were associated with high proliferative index, higher grade and Oestrogen Receptor (ER)- negative tumours and represent a strong prognostic factor for certain breast cancer subtypes, especially the Triple-Negative Breast Cancer (TNBC) [5,6]. Currently, TIL estimation is not part of the pathology reporting protocols for breast carcinoma and the role of TIL in the prognosis of untreated patients is unknown. The present study evaluates TILs in Indian breast carcinoma patients and their correlation to known prognostic factors and outcomes in patients of early breast carcinoma who have undergone definitive surgical intervention with curative intent. MATERIALS AND METHODS A retrospective and prospective Cohort study was carried out at a large tertiary care oncology referral centre of Armed Forces Medical College, Pune, Maharashtra, India. Seventy-five patients of early breast carcinoma who underwent definitive surgical excision of the tumour in the form of Modified Radical Mastectomy (MRM) or Breast Conservation Surgery (BCS) between January 2014 to November 2017 were included. The inclusion criteria were Histopathological Examination (HPE) proven cases of Breast carcinoma who have undergone definitive surgery for breast carcinoma with information on pathological grade and TNM stage of disease. Patients with secondary malignant lesions of breast, incomplete clinical, prognostic and follow-up information and those exhibiting neo-adjuvant chemotherapy prior to surgery were excluded. Prior approval of the Institutional Ethics Committee was obtained vide AFMC IEC/141/2017 dt 28 Sep 2017. For all cases, the HPE slides were re-examined for the grade, stage and tumour type and one representative FFPE block with predominantly viable tumour tissue identified for IHC. Tumours were graded by Nottingham modification of the Bloom-Richardson system [7] and staged using the TNM system as per the 8 th edition of American Joint Committee on Cancer (AJCC) staging manual [8]. The cases were categorised into molecular subtypes as Luminal A (ER + and/or PR+, Ki67 < 20% and HER2-), Luminal B (ER + and/ or PR+, Ki67 > 20% and/or HER2+), HER2-positive (ER-, PR- and DEEP KUMAR RAMAN 1 , NARESH GUPTA 2 , SHANTANU KHANNA 3 , RAJNEESH JOSHI 4 , REENA BHARADWAJ 5 Keywords: Breast neoplasms, Prognosis, Recurrence, T-Lymphocyte subsets ABSTRACT Introduction: Breast cancer is the most commonly diagnosed cancer in women worldwide with over 2.1 million new cases per year. While hereditary and genetic factors as well as many conventional prognostic markers are well established in clinical practice, the role of host immunity in the determining the prognosis is still not clearly understood. Aim: To evaluate the association of Tumour-Infiltrating Lymphocytes (TILs) with known prognostic markers and disease outcome parameters in a cohort of breast carcinoma patients from India. Materials and Methods: Formalin Fixed Paraffin Embedded (FFPE) sections from patients of breast carcinoma who underwent definitive surgery were stained with anti-CD8 antibody by Immunohistochemistry (IHC) and mean number of Intratumoural (iTILs), Stromal (sTILs) and Total (tTILs) TILs ascertained. These were compared with known prognostic markers and survival data using median and inter-quartile range. Wilcoxon-Mann-Whitney test was used. Results: 75 of the 184 cases of breast carcinoma that met the inclusion criteria were included in the study. A statistically significant association was seen with iTIL (p=0.041) and tTIL (p=0.037) for patients with relapse. No association, however, was seen with hormonal receptor status, Her2 neu positivity, the Intrinsic molecular subtypes or other known prognostic markers like the grade, tumour size, nodal metastasis and TNM stage. Conclusion: The present study shows that higher levels of iTIL and tTIL but not sTIL are associated with a lower rate of recurrence and have a better prognosis. TILs appear to be independent markers as none of the known prognostic markers like tumour size, lymph node status are associated with TILs in present cohort.