Korean J Urol.  2015 Jan;56(1):31-40. 10.4111/kju.2015.56.1.31.

Expression of survivin in squamous cell carcinoma and transitional cell carcinoma of the urinary bladder: A comparative immunohistochemical study

• Makboul R
• Refaiy AE
• Badary FA
• Abdelkawi
• Merseburger AS
• Mohammed R

• KMID: 2070266
• DOI: http://doi.org/10.4111/kju.2015.56.1.31

Abstract

PURPOSE
To compare the expression of survivin and its association with clinicopathological criteria in major types of urinary bladder carcinoma, specifically, transitional cell carcinoma with and without squamous differentiation and squamous cell carcinoma.
MATERIALS AND METHODS
Immunohistochemical staining for survivin and Ki67 was performed on paraffin-embedded sections of 104 carcinomas: 52 transitional cell carcinoma, 20 transitional cell carcinoma with squamous differentiation, and 32 squamous cell carcinoma. Expression of survivin in >10% of tumor cells was described as altered survivin status. Ki67 staining in >20% of tumor cells was described as a high proliferation index.
RESULTS
Altered survivin expression was detected in 60/104 specimens (58%) and was significantly more frequent in transitional cell carcinoma (78%) than in squamous cell carcinoma (38%) or transitional cell carcinoma with squamous differentiation (40%) (p<0.0001). In transitional cell carcinoma but not in squamous cell carcinoma, altered survivin status was associated with higher tumor grade, higher proliferation index, and recurrence. In the whole specimens, altered survivin expression was significantly associated with advanced stage (p<0.001), recurrence (p=0.005), distant metastasis (p<0.001), and death (p=0.001). In the multivariate analysis, altered survivin was an independent poor prognostic factor for recurrence.
CONCLUSIONS
Unlike in transitional cell carcinoma, alteration of survivin expression in squamous cell carcinoma occurs less frequently and is not associated with features of tumor aggression or patient outcome. These findings raise a question: are urinary bladder carcinoma patients with squamous cell carcinoma type suitable candidates for survivin vaccine? This is an important question to be answered before approving the vaccine in management.

Keyword

Squamous cell carcinoma; Transitional cell carcinoma; Urinary bladder; Vaccines

MeSH Terms

Carcinoma, Squamous Cell/*genetics
Carcinoma, Transitional Cell/*genetics
Female
Humans
Inhibitor of Apoptosis Proteins/genetics/*metabolism
Ki-67 Antigen/metabolism
Male
Middle Aged
Multivariate Analysis
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Treatment Outcome
Tumor Markers, Biological
Urinary Bladder/pathology
Urinary Bladder Neoplasms/*genetics
Inhibitor of Apoptosis Proteins
Ki-67 Antigen
Tumor Markers, Biological

Figure

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  Fig. 1 (A, B) Two sections from two high-grade transitional cell carcinoma tumors stained with antisurvivin showing positive nuclear staining in most tumor cells (scale: A, 100 µm; B, 50 µm). (C, D) Two sections from moderately differentiated squamous cell carcinomas stained with antisurvivin antibody showing nuclear staining pattern in panel C and only cytoplasmic reactivity in panel D (scale: C and D, 50 µm).

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  Fig. 2 (A, B) Two sections from a low-grade transitional cell carcinoma (TCC) and a high-grade TCC, respectively, stained with anti-Ki67 antibody showing positive nuclear staining. Ki67-LI is low in panel A and is high in panel B (scale: A and B, 200 µm). (C, D) Two sections from a well-differentiated and a moderately differentiated SCC stained with anti-Ki67 antibody showing low Ki67-LI in panel C and high Ki67-LI in panel D (scale: C, 50 µm; D, 200 µm).

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  Fig. 3 (A, B) Kaplan-Meier survival curves showing a significant association between altered survivin expression and shorter recurrence-free and distantmetastasis-free interval. (C, D) Kaplan-Meier survival curves showing a significant association between combined altered survivin expression and high Ki67% with recurrence and with distant metastasis.

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