TP53 mutations and pathologic complete response to neoadjuvant cisplatin and fluorouracil chemotherapy in resected oral cavity squamous cell carcinoma.
PURPOSE To find out if TP53 functional status predicts response to neoadjuvant chemotherapy and thus may be helpful during treatment decision making of oral cavity squamous cell carcinoma (SCC) patients. PATIENTS AND METHODS We analyzed the predictive value of TP53 mutations and their functional status on the basis of the transactivation activity of p53 mutant proteins in 53 pretreatment biopsies of oral cavity SCC patients receiving primary cisplatin and fluorouracil chemotherapy followed by surgery. Results The surgical specimens showed that 15 patients (28%) achieved a pathologic complete remission (pCR) at both T and N sites, and 38 patients had residual tumor cells. Among the 53 pretreatment biopsies, 24 (45%) displayed TP53 mutations: 22 single-nucleotide substitutions and two deletions. According to functional status that could be determined only for the 22 substitutions, 21 mutations were nonfunctional and one was partially functional. TP53 mutation was found in four (27%) of 15 patients who achieved a pCR and in 20 (53%) of 38 nonresponder patients; the difference was not statistically significant (P = .12). In contrast, two (14%) of 14 cases with pCR carried a nonfunctional TP53 mutation, a frequency significantly less than that found in the nonresponders (19 [51%] of 37; P = .02). TP53 mutation predicted pCR in four (17%) of 24 patients and a nonfunctional mutation in only two (9%) of 22 patients. CONCLUSION The results indicate that the loss of function (transactivation activities) of p53 mutant proteins may predict a significant low pCR rate and suboptimal response to cisplatin-based neoadjuvant chemotherapy in patients with oral cavity SCC.
Perrone
Federica
F
Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy.
Bossi
Paolo
P
Cortelazzi
Barbara
B
Locati
Laura
L
Quattrone
Pasquale
P
Pierotti
Marco A
MA
Pilotti
Silvana
S
Licitra
Lisa
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009154:Mutation; D020360:Neoadjuvant Therapy; D019647:Oral Surgical Procedures; D018579:Patient Selection; D011237:Predictive Value of Tests; D013997:Time Factors; D015533:Transcriptional Activation; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil