Association of Ki67 Antigen With Mitotic Count, Tumor Size, and Necrosis in Neuroendocrine Tumors of Lung

Introduction Lung cancer is considered as one of the most common cancers worldwide and one of the five most prevalent cancers in Iran (1). Unfortunately, most patients are diagnosed in advanced stages and thus the survival rate of 5-year-old cancer is up to 15% (2). Pathologically, neuroendocrine tumors arise in many organs and share common pathological features although there is a specific system for staging and grading in each organ (3). Lung neuroendocrine tumors are classified into four categories according to the World Health Organization (WHO) classification (2004). This classification is based on morphology, mitotic counts, and necrosis and includes typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). However, there are diagnostic problems in this method due to common cytological features between AC and LCNEC, as well as LCNEC and SCLC and thus its efficacy in terms of prognostic value was rejected after several studies (4). According to this classification, TC and AC diagnosis are based on the number of mitoses and the presence or absence of necrosis in hematoxylin-eosin-stained tissues, but mitotic counting is difficult and time-consuming and differentiating between pyknotic and mitotic nuclei can also be difficult. In addition, determining the presence or absence of necrosis can be complicated (5). The Ki67 antigen, as a nuclear Ag and only present in proliferative cells, is studied in these tumors while its clinical application is not well-defined yet. Further, its diagnostic use in separating TC and AC from the nonsurgical samples of SCLC is regarded as its known role. This antigen is even used to separate the TCs from ACs. The application of new diagnostic techniques such as biochemistry-immunohistochemistry and molecular methods has a significant effect on the identification, diversity of histopathologic species, clinical behavior, and the prognosis of these tumors. Considering the biological behavior of the tumors based on their position and the degree of differentiation, the new classification of WHO is considered more beneficial in terms of both clinical and prognostic factors (6). Abstract Objectives: Lung cancer is the most prevalent cancer in the world and one of the five most common cancers in Iran. The level of Ki67 biomarker is related to any of the factors affecting the grading of neuroendocrine lung tumors, which is used as one of the grading criteria and a criterion for assessing and predicting survival and prognostic factors. The aim of this study was to investigate the relationship between Ki67 antigen incidence and mitotic count, necrosis, tumor size in the neuroendocrine tumors of the lung. Materials and Methods: The samples of this analytical descriptive study, including the neuroendocrine tumors of the lung in paraffin blocks were chosen from the pathology archive of Imam Reza hospital collected during the last 10 years. Ki67 antigen immunohistochemical procedures, along with mitotic count and necrosis were performed by a collaborator pathologist. The collected data were analyzed by SPSS software and P-value less than 0.05 was considered a statistically significant level. Results: The mean incidence of Ki67 antigen in the neuroendocrine tumors of the lung was 57.7± 6.5 and the lowest and highest incidence was 1% and 90%, respectively. In addition, the relationship between Ki67 antigen incidence and mitotic count and necrosis were significant while no significant relationship was observed between Ki67 antigen incidence and tumor size in typical carcinoid tumors. Conclusions: Overall, the Ki67 antigen is regarded as a useful and essential tool for grading neuroendocrine lung tumors.