Histological effects and predictive biomarkers of TPP induction chemotherapy for oral carcinoma

Abstract

Hamakawa H, Bao Y, Takarada M, Tanioka H: Histological effects and predictive biomarkers of TPP induction chemotherapy for oral carcinoma. J Oral Pathol Med 1998; 27: 87–94. © Munksgaard, 1998. The effects of an induction chemotherapy with THP‐adriamycin, cisplatin, and peplomycin (TPP) were studied in 32 patients with operable oral cancer. The histological evaluation according to the Shimozato‐Oboshi classification was Grade (G) IV in ten cases (31.3%), GUI in one case, and Glib in four cases. Induction of apoptosis and differentiation‐inducing effects, hyperkeratinization or bone formation, were observed in some cases. The overall clinical response rate and histological response rate were 63% and 47%, respectively. Grade III was obtained in seven metastatic lymph nodes of three patients. The expressions of PCNA, p53, and AgNORs before and after chemotherapy were studied. The prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors (GUI, IV) was significantly lower than that of the poorly responsive tumors (G0‐Ilb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P < 0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the efficacy of TPP chemotherapy.

Chromosomal Instability in Oral Cancer Cells

“…Tumor suppressor genes-including FHIT, RB1, TP53, and CDKN2A (p16 INK4A )-have been shown to play key roles in HNSCC tumorigenesis (Virgilio et al, 1996;Koontongkaew et al, 2000;Nakahara et al, 2000). Specifically, loss of TP53 function has been shown to correlate with poor response to chemotherapeutic agents such as platinum drugs and fluorouracil, as well as with resistance to radiotherapy (O'Connor et al, 1993;Hamakawa et al, 1998;Temam et al, 2000). In addition, loss of 3p14 and/or 9p21 is considered to be an early event in HNSCC, and, along with TP53 alterations, has been a useful marker for monitoring increased recurrence risk (Brennan et al, 1995;Califano et al, 1996;Gollin, 2001;Rosin et al, 2002).…”