Biological markers as indicators of pathological response to primary chemotherapy in oral-cavity cancers.
The predictive role in terms of pathological response and prognostic role of biomarkers such as GST-pi, p53, bcl-2 and bax expression, immuno-histochemically detected, and of the S-phase cell fraction, autoradiographically determined as thymidine labeling index (TLI), were investigated within a prospective randomized phase III clinical trial on squamous-cell carcinoma of the oral cavity, including surgery or primary chemotherapy (PCT), which foresaw the prospective determination of biological markers. Pathological response was defined as the achievement after PCT of a pathological complete remission or the presence of microresidual disease. The study was performed on tumors obtained from a series of 100 previously untreated patients with resectable T2-4N0-2M0 carcinoma. All biomarkers were unrelated, except for an inverse relation between TLI and GST-pi and a direct relation between bcl-2 and bax expression. In patients treated with surgery alone, 3-year disease-free survival (DFS) appeared to be weakly, but not significantly, related only to GST-pi and p53 expression. In patients treated with PCT, pathological response and DFS were independent of p53 expression and cell proliferation. Conversely, low GST-pi and bax expression were indicative of pathological response but lost relevance as predictors of DFS, whereas absence of bcl-2 was associated with high probability of 3-year DFS in the overall series as well as in non-responding patients. Within this latter sub-set, all patients with bcl-2-positive tumors relapsed within 1 year of surgery, whereas a 60% probability of 3-year DFS was observed for patients with bcl-2-negative tumors (p = 0.02). This interim analysis appears to indicate that some biofunctional markers can provide information on pathological response to PCT and could help in understanding treatment efficacy at a cellular level.
Costa
A
A
Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. acosta@istitutotumori.mi.it
Licitra
L
L
Veneroni
S
S
Daidone
M G
MG
Grandi
C
C
Cavina
R
R
Molinari
R
R
Silvestrini
R
R
D015415:Biomarkers / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016196:S Phase; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D015415:Biomarkers; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase