Different protein expression associated with chemotherapy response in oropharyngeal cancer according to HPV status

BMC Cancer

Sang-Hee Cho⁵  Yoo-Duk Choi⁴  Hoi-Soon Lim¹  Jae-Uk Jeong³  Woong-Ki Chung³  Sang-Chul Lim²  Tae-Mi Yoon²  Joon-Kyoo Lee²  Dong-Hoon Lee²  Ik-Joo Chung⁵  Woo-Kyun Bae⁵  Jun-Eul Hwang⁵  Hyun-Jeong Shim⁵  Karham Kim⁵  Myung-Seo Ki⁵  Min-Jee Kim⁵ 

[1]Department of Dentistry, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

[2]Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

[3]Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

[4]Department of Pathology, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea

[5]Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo 519-763, Republic of Korea

关键词: bcl-2;    Beta tubulin;    p53;    Chemotherapy;    p16;    HPV;    Oropharyngeal cancer;   

Others  :  1118423
DOI  :  10.1186/1471-2407-14-824

 received in 2014-06-08, accepted in 2014-10-24,  发布年份 2014

【 摘 要 】

Backgound

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).

Conclusion

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.

【 授权许可】

   
2014 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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