Different protein expression associated with chemotherapy response in oropharyngeal cancer according to HPV status.
BACKGROUND
Oropharyngeal cancer (OPC) associated with human papilloma virus (HPV OPC) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, β-tubulin, bcl-2 and ERCC 1, which are well-known biomarkers to predict the chemotherapy response, according to HPV status in OPC patients.


METHODS
Patients who treated with at least 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced oropharyngeal cancer were reviewed. HPV PCR and immunohistochemical stain was done in paraffin embedded tumor tissue and evaluated the relation with the chemotherapy response and survival outcomes according to HPV status.


RESULTS
Seventy-four patients were enrolled for this study and all patients received induction chemotherapy with docetaxel, 5-FU and cisplatin. After induction chemotherapy, complete response (CR) was shown in 22 patients (30%) and partial response (PR) in 46 patients (62%). HPV + was detected in 21 patients (28%), while 35 patients (47%) showed p16+ expression by IHC analysis. p16 positive patients showed better overall response, PFS and OS than p16 negative patients. p53 and class III beta-tubulin expression were significantly higher in HPV- and p16- than HPV + and p16+ patients. Conversely, bcl-2 expression was greater in HPV + or p16+ than HPV- or p16- patients. ERCC1 expression did not differ significantly according to HPV status. In multivariate analyses, early T stage (p = 0.036) and good PS (PS 0) (p = 0.029) showed a better 3Y-PFS rate, and low p53 expression (p = 0.012) and complete response after induction chemotherapy (p = 0.026) were highly associated with 3Y-OS rate. Low expression of p53 and p16 positive patients showed significantly prolonged OS than others (p = 0.010).


CONCLUSIONS
P53, class III beta-tubulin and bcl-2 were differently expressed in OPC according to HPV status and present study suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC. Among these biomarkers, p53 is the strongest prognostic marker in OPC and p53 in addition to p16 support the rationale to study of de-escalation strategy for OPC.
Min-Jee
MJ
Kim
Myung-Seo
MS
Ki
Karham
K
Kim
Hyun-Jeong
HJ
Shim
Jun-Eul
JE
Hwang
Woo-Kyun
WK
Bae
Ik-Joo
IJ
Chung
Dong-Hoon
DH
Lee
Joon-Kyoo
JK
Lee
Tae-Mi
TM
Yoon
Sang-Chul
SC
Lim
Woong-Ki
WK
Chung
Jae-Uk
JU
Jeong
Hoi-Soon
HS
Lim
Yoo-Duk
YD
Choi
Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo 519-763, Republic of Korea. shcho@jnu.ac.kr.
Sang-Hee
SH
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C071447:ERCC1 protein, human; D004720:Endonucleases