Is Ki-67 (proliferation marker) elevated in neuroendocrine tumors or small cell lung cancer?

From the Guidelines

Ki-67 is typically elevated in both neuroendocrine tumors and small cell carcinomas, serving as an important proliferation marker that helps determine tumor grade and aggressiveness. In neuroendocrine tumors, Ki-67 levels directly correlate with tumor grade - low-grade tumors (G1) show Ki-67 indices <3%, intermediate-grade (G2) show 3-20%, and high-grade (G3) show >20% 1. Some key points to consider are:

• Small cell carcinomas, being highly aggressive neuroendocrine neoplasms, characteristically display very high Ki-67 proliferation indices, often exceeding 50-60% and sometimes reaching nearly 100% 1.
• This elevated Ki-67 expression reflects the rapid cell division and aggressive nature of these tumors, which explains their typically poor prognosis and rapid growth.
• Pathologists routinely use Ki-67 immunohistochemical staining to help distinguish between tumor grades and types, guiding treatment decisions and providing prognostic information 1.
• The higher the Ki-67 index, the more aggressive the tumor behavior tends to be, often necessitating more intensive treatment approaches.
• Ki-67 proliferation index may offer a more accurate distinction between SCLCs with a high index of . 50% to 70% and carcinoids with a low index of 5% to 15% 1.
• The use of Ki-67 as a prognostic marker is supported by the fact that increased mitotic rate and high Ki-67 index are associated with a more aggressive clinical course and worse prognosis in neuroendocrine tumors 1.

From the Research

Ki-67 Expression in Neuroendocrine Tumors and Small Cell Lung Cancer

• Ki-67 is a marker of cellular proliferation and has been studied as a prognostic biomarker in various types of tumors, including neuroendocrine tumors and small cell lung cancer 2.
• In pulmonary neuroendocrine neoplasms, a high Ki-67 index has been associated with poorer overall survival and recurrence-free survival 2.
• The 2010 WHO classification divides gastroentero-pancreatic neuroendocrine tumors into two main subgroups: neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), based on Ki-67 levels, with NET having low (<20%) Ki-67 values and NEC having high Ki-67 levels (>20%) 3.
• In small cell lung cancer, which is a type of neuroendocrine carcinoma, Ki-67 levels are typically high, indicating a high proliferation rate 3, 2.

Prognostic Value of Ki-67 in Neuroendocrine Tumors

• Ki-67 has been shown to be a prognostic factor in neuroendocrine tumors, with higher Ki-67 indices associated with poorer outcomes 4, 5, 6.
• In pancreatic neuroendocrine neoplasms, Ki-67 has been found to be a reliable prognostic marker, with higher Ki-67 values indicating a higher risk of disease progression 6.
• However, the prognostic value of Ki-67 can vary depending on the specific type of neuroendocrine tumor and the stage of the disease 4, 5.

Ki-67 and Response to Chemotherapy

• Ki-67 has been studied as a potential marker to predict response to chemotherapy in neuroendocrine tumors, but the results have been inconsistent 5.
• While some studies have found that higher Ki-67 indices are associated with a better response to chemotherapy, others have found that Ki-67 is not a reliable predictor of response 5.