Prediction of TP53 status for primary cisplatin, fluorouracil, and leucovorin chemotherapy in ethmoid sinus intestinal-type adenocarcinoma.
OBJECTIVE
To assess the role of TP53 status in predicting pathologic complete remission after primary chemotherapy in patients with ethmoidal intestinal-type adenocarcinoma (ITAC).


METHODS
Thirty patients with ethmoidal ITAC enrolled onto a phase II study received chemotherapy with cisplatin, fluorouracil, and leucovorin (PFL) followed by surgery and radiation. On surgical specimens, absence of viable tumor cells was defined as pathologic complete remission (pCR). TP53 status/p53 function, analyzed on pretreatment biopsies, were retrospectively correlated with pathologic results and patient outcome.


RESULTS
Twelve patients achieved a pCR; 18 patients did not (overall response rate, 40%). In patients with wild-type (wt) TP53 or functional p53 protein, the pCRs were 83% and 80%, respectively; in patients with mutated TP53 or impaired p53 protein, pCRs were 11% and 0%, respectively (P < or = .0001). At a median 55-month follow-up, all pCR patients were disease-free; 44% of nonresponding patients experienced relapse (P = .0061).


CONCLUSIONS
The results indicate the existence of two genetic ITAC subgroups, defined by differences in TP53 mutational status or protein functionality, that strongly influence pathologic response to primary chemotherapy and, ultimately, prognosis. PFL seems to be highly effective in terms of pCR and disease-free survival in the presence of a wt or a still-efficient p53 protein, even when encoded by a mutated TP53 gene (eg, early-stop codon mutation), but ineffective in ITACs carrying a disabled p53 protein. Whether this model is extensible to other head and neck cancers needs appropriate investigation.
Licitra
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L
Medical Oncology Department, Head and Neck Unit, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. lisa.licitra@istitutotumori.mi.it
Suardi
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Bossi
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Mariani
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Quattrone
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Lo Vullo
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Oggionni
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Olmi
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Cantù
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Pierotti
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D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005005:Ethmoid Sinus / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005544:Forecasting; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil