期刊论文详细信息
Journal of Translational Medicine
Cytosolic phosphorylated EGFR is predictive of recurrence in early stage penile cancer patients: a retropective study
Renato Franco5  Paolo A Ascierto6  Gaetano Facchini6  Sabino De Placido7  Gerardo Botti5  Pasquale Rescigno7  Rossella Di Trolio6  Daniela Terracciano7  Gabriella Gaudioso5  Matteo Ferro4  Giuseppe Quarto1  Giuseppe Pannone2  Vincenzo Gigantino5  Guru Sonpavde3  Carlo Buonerba7  Sisto Perdonà1  Giuseppe Di Lorenzo7 
[1] Urology Division, ISTITUTO NAZIONALE TUMORI "FONDAZIONE G. PASCALE"-IRCCS, Naples, Italy;Department of Surgical Sciences; Section of Anatomic Pathology; Second Section of Oral Pathology, University of Foggia, Foggia, Italy;University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL, USA;Division of Urology, European Institute of Oncology, Milan, Italy;Pathology Unit, ISTITUTO NAZIONALE TUMORI "FONDAZIONE G. PASCALE"- IRCCS, Naples, Italy;Division of Medical Oncology, Department of Urology and Gynecology, ISTITUTO NAZIONALE TUMORI "FONDAZIONE G. PASCALE"- IRCCS, Naples, Italy;Genitourinary Cancer Section and Rare-Cancer Center, Medical Oncology Division, University Federico II, Napoli, Italy
关键词: Tissue micro-array (TMA);    Penile cancer;    Immunohistochemistry;    Phospo-EGFR;    Epidermal growth factor receptor (EGFR) expression;   
Others  :  827306
DOI  :  10.1186/1479-5876-11-161
 received in 2013-05-14, accepted in 2013-06-13,  发布年份 2013
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【 摘 要 】

Background

Penile cancer (PC) is a rare tumor, and therapeutic options are limited for this disease, with an overall 5-year overall survival around 65-70%. Adjuvant therapy is not recommended for patients with N0-1 disease, despite up to 60% of these patients will die within 5 years from diagnosis.

Methods

Medical records of all patients who underwent radical surgery at University Federico II of Naples and at National Tumor Institute “Pascale” of Naples for early squamous cell carcinoma of the penis from January, 2000 to December, 2011 were retrieved. Paraffin wax embedded tissue specimens were retrieved from the pathology archives of the participating Institutions for all patients. Expression of p-EGFR, EGFR and positivity to HPV were evaluated along with other histological variables of interest. Demographic data of eligible patients were retrieved along with clinical characteristics such as type of surgical operation, time of follow up, time of recurrence, overall survival. A multivariable model was constructed using a forward stepwise selection procedure.

Results

Thirty eligible patients were identified. All patients were positive for EGFR by immunohistochemistry, while 13 and 16 were respectively positive for nuclear and cytosolic p-EGFR. No EGFR amplification was detected by FISH. Eight patients were positive for high-risk HPV by ISH. On univariable analysis, corpora cavernosa infiltration (OR 7.8; 95% CI = 0,8 to 75,6; P = 0,039) and positivity for cytosolic p-EGFR (OR 7.6; 95% CI =1.49 to 50; P = 0.009) were predictive for recurrence, while only positivity for cytosolic p-EGFR (HR =9.0; 95% CI 1.0-100; P = 0,0116) was prognostic for poor survival.

Conclusion

It is of primary importance to identify patients with N0-1 disease who are at increased risk of recurrence, as they do not normally receive any adjuvant therapy. Expression of p-EGFR was found in this series to be strongly related to increase risk of recurrence and shorter overall survival. This finding is consistent with the role of p-EGFR in other solid malignancies. Integration of p-EGFR with classic prognostic factors and other histology markers should be pursued to establish optimal adjuvant therapy for N0-1 PC patients.

【 授权许可】

   
2013 Di Lorenzo et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Sonpavde G, Pagliaro LC, Buonerba C, Dorff TB, Lee RJ, Di Lorenzo G: Penile cancer: current therapy and future directions. Ann Oncol 2013, 24(5):1179-1189.
  • [2]Verhoeven RH, Janssen-Heijnen ML, Saum KU, Zanetti R, Caldarella A, et al.: Population-based survival of penile cancer patients in Europe and the United States of America: no improvement since 1990. Eur J Cancer 2013, 49(6):1414-21.
  • [3]Di Lorenzo G, Buonerba C, Federico P, Perdonà S, Aieta M, et al.: Cisplatin and 5-fluorouracil in inoperable, stage IV squamous cell carcinoma of the penis. BJU Int 2012, 110(11):E661-6.
  • [4]Pizzocaro G, Algaba F, Horenblas S, Solsona E, Tana S, et al.: EAU penile cancer guidelines 2009. Eur Urol 2010, 57(6):1002-12.
  • [5]Kattan MW, Ficarra V, Artibani W, Cunico SC, et al.: Nomogram predictive of cancer specific survival in patients undergoing partial or total amputation for squamous cell carcinoma of the penis. J Urol 2006, 175(6):2103-8.
  • [6]Lont AP, Kroon BK, Horenblas S, Gallee MP, Berkhof J, et al.: Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer 2006, 119(5):1078-81.
  • [7]Gunia S, Jain A, Koch S, Denzinger S, Götz S, Niessl N, May M: Periostin expression correlates with pT-stage, grading and tumour size, and independently predicts cancer-specific survival in surgically treated penile squamous cell carcinomas. J Clin Pathol 2013. Epub ahead of print
  • [8]Gunia S, Kakies C, Erbersdobler A, Hakenberg OW, Koch S, et al.: Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis. J Clin Pathol 2012, 65(3):232-6.
  • [9]Kayes OJ, Loddo M, Patel N, Patel P, Minhas S, et al.: DNA replication licensing factors and aneuploidy are linked to tumor cell cycle state and clinical outcome in penile carcinoma. Clin Cancer Res 2009, 15(23):7335-44.
  • [10]Stankiewicz E, Prowse DM, Ng M: Alternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomas. PLoS One 2011, 6(3):e17517.
  • [11]Lavens N, Gupta R, Wood LA: EGFR overexpression in squamous cell carcinoma of the penis. Curr Oncol 2010, 17(1):4-6.
  • [12]Kanematsu T, Yano S, Uehara H, Bando Y, Sone S: Phosphorylation, but not overexpression, of epidermal growth factor receptor is associated with poor prognosis of non-small cell lung cancer patients. Oncol Res 2003, 13(5):289-98.
  • [13]Magkou C, Nakopoulou L, Zoubouli C, Karali K, Theohari I, et al.: Expression of the epidermal growth factor receptor (EGFR) and the phosphorylated EGFR in invasive breast carcinomas. Breast Cancer Res 2008, 10(3):R49. BioMed Central Full Text
  • [14]Aquino G, Pannone G, Santoro A, Liguori G, Franco R, et al.: pEGFR-Tyr 845 expression as prognostic factors in oral squamous cell carcinoma: a tissue-microarray study with clinic-pathological correlations. Cancer Biol Ther 2012, 13(11):967-77.
  • [15]Sobin LH, Wittekind C: TNM Classification of Malignant Tumours. : Wiley; 2002.
  • [16]Broders AC: SQUAMOUS-CELL EPITHELIOMA OF THE SKIN: A STUDY OF 256 CASES. Ann Surg 1921, 73(2):141-60.
  • [17]Backes DM, Kurman RJ, Pimenta JM, Smith JS: Systematic review of human papillomavirus prevalence in invasive penile cancer. Cancer Causes Control 2009, 20(4):449-57.
  • [18]Kong CS, Narasimhan B, Cao H, Kwok S, Erickson JP, et al.: The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys 2009, 74(2):553-61.
  • [19]Necchi A, Nicolai N, Colecchia M, Catanzaro M, Torelli T, et al.: Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol 2011, 29:e650-2.
  • [20]Di Lorenzo G, Buonerba C, Gaudioso G, et al.: EGFR mutational status in penile cancer. Expert Opin Ther Targets 2013, 17:501-5.
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