IMP3, a Prognostic Biomarker for Disease Progression in Superficial Urothelial Carcinoma
Kristine M Cornejo, Zhong Jiang, Christopher Owens. University of Massachusetts Medical School, Worcester, MA
Background: The majority of urothelial carcinomas (UC) are superficial which includes the tumor, node and metastasis (TNM) categories of Ta (non-invasive papillary carcinoma), Tis (flat carcinoma in situ) and T1 (tumor invading the lamina propria) on initial biopsy. However, the biological behavior varies from relatively indolent to overtly aggressive. Treatment is based upon tumor stage and histologic grade with the majority of low grade and stage lesions treated with local resection and close follow-up and/or intravesical therapy, versus high grade and stage lesions are treated with more aggressive therapy such as cystectomy or radiation with chemotherapy. Tumor grade and stage alone is limited in predicting disease progression. Therefore, a biomarker that can identify superficial UC with a high probability of progressing to muscle invasive disease (T2-T4) would be clinically useful as more aggressive therapy or closer observation may be initiated. IMP3, an oncofetal protein has been found to predict aggressive behavior in certain malignant neoplasms. The aim of this study was to investigate the expression of IMP3 in superficial UC to determine whether it can serve as a prognostic biomarker to predict progression to muscle invasive disease.
Design: A total of 81 cases (biopsy n=81), including 50 non-invasive papillary carcinoma (Ta), 9 flat UC in situ (Tis) and 22 invasive UC to the lamina propria (T1) were obtained from the surgical pathology files of a tertiary Medical Center between 2003-2009. Follow-up ranged from 4 to 107 months with a mean of 38.6 months. Disease progression was defined as muscle invasive disease (T2-T4) from a superficial UC (Ta, Tis or T1) on initial diagnostic biopsy.
Results: Twenty-seven of 81 (33%) superficial UC expressed IMP3. IMP3 positivity was detected in 6 of 50 (12%) Ta, 5 of 9 (56%) Tis and 16 of 22 (73%) T1 UC cases. IMP3 expression was detected in 8 of 11 (73%) cases with disease progression which was statistically significant (P<0.01). In addition, the 2 cases with metastatic disease were both IMP3 positive. Of the 81 cases, 12 were treated with cystectomy or radiation with chemotherapy, of which 10 (83%) cases expressed IMP3.
Conclusions: Our findings indicate that IMP3 can be used as a prognostic marker at the time of initial diagnosis to identify a subgroup of patients with superficial UC with a high potential of progressing to muscle invasive disease. Therefore, these patients may benefit from early intensive therapy or stringent monitoring.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 204, Tuesday Afternoon