The prognostic value of Ki-67 expression in penile squamous cell carcinoma
- Elzbieta Stankiewicz1,
- Mansum Ng1,
- Jack Cuzick2,
- David Mesher2,
- Nick Watkin3,
- Wayne Lam3,
- Cathy Corbishley4,
- Daniel M Berney1,5
- 1Department of Molecular Oncology, Barts Cancer Institute, London, UK
- 2Cancer Research UK Centre for Cancer Prevention, Queen Mary University of London, London, UK
- 3Department of Urology, St George's Hospital, London, UK
- 4Department of Cellular Pathology, St George's Hospital, London, UK
- 5Department of Histopathology, Royal London Hospital, London, UK
- Correspondence to Elzbieta Stankiewicz, Department of Molecular Oncology, Barts Cancer Institute, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK;
Contributors ES and DMB contributed to study design, acquisition and analysis of data and manuscript preparation. MN and WL contributed to acquisition and analysis of data. CC and NW contributed to technical and material support, acquisition of data and critical revision of the manuscript for important intellectual content. JC and DM contributed to statistical analysis.
- Accepted 16 February 2012
- Published Online First 23 March 2012
Aims To determine whether Ki-67 immunoexpression in penile squamous cell carcinoma (PSCC) has a prognostic value and correlates with lymph node metastasis, human papillomavirus (HPV) infection and patient survival.
Methods 148 formalin-fixed paraffin-embedded PSCC samples were tissue-microarrayed, including 97 usual-type SCCs, 17 basaloid, 15 pure verrucous carcinomas, 2 warty and 17 mixed-type tumours. All samples were immunostained for Ki-67 protein. HPV DNA was detected with INNO-LiPA assay. Follow-up data were available for 134 patients.
Results Ki-67 was strongly expressed in 57/148 (38.5%) of PSCCs. Different cancer subtypes showed significant difference in Ki-67 expression (p<0.0001) with highest positivity in basaloid, 16/17 (94%), followed by usual type, 38/97 (39%) and lack of Ki-67 positive cases within verrucous tumours, 0/15. Ki-67 positively correlated with high-risk HPV (p<0.0001) and showed good specificity (84%) but low sensitivity (61%) for high-risk HPV detection. Ki-67 protein strongly positively correlated with tumour grade (p<0.0001) but not with stage (p=0.2193), or lymph node status (p=0.7366). Ki-67 showed no prognostic value for cancer-specific survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.54) or overall survival (HR=1.00, 95%, CI 0.99 to 1.02, p=0.45). High tumour stage, lymph node metastasis, high tumour grade and age at diagnosis were all independent prognostic factors for cancer-specific survival and overall survival.
Conclusions Ki-67 is only a moderate surrogate marker for HPV infection in PSCC. It does not show prognostic value for cancer-specific survival and overall survival in PSCC.
- penile squamous cell carcinoma
- lymph node metastasis
- cancer research
- urinary tract tumours
- genitourinary pathology
- urogenital pathology
This work should be attributed to Barts Cancer Institute, Queen Mary University of London, Molecular Oncology, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
Funding This project is supported by The Jean Shanks Foundation and Orchid.
Competing interests None.
Ethics approval Ethics approval was provided by East London and The City Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.