Reduction of Proliferation and Induction of Apoptosis are Associated with Shrinkage of Head and Neck Squamous Cell Carcinoma due to Neoadjuvant Chemotherapy


Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is usedas the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by othermeans. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facialorgans of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materialsand
Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapywere screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of somecell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX,BCL2) associated proteins in the same set of samples.
Results: Significant decrease in proliferation index andincrease in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observedin post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged,p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and inductionof apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulationof apoptosis in response to therapy.
Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteinsand apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.