[Study of Her2/neu protein over expression frequency and its relationship with grade, stage in patients with non metatstatic transitional cell carcinoma and disease free survival]

ABSTRACT

HER2 over-expression has been identified in a variety of malignant tumors including bladder transitional carcinoma. In some researches H.ER2 was detected in 10%-50% of muscle invasive bladder cancers. In this study we evaluated the correlation between HER2 over-expression and pathological characteristics as well as its impact on the disease free survival [DFS] of patients with non-metastatic bladder transitional carcinoma. Study of Her2/neu Protein over Expression Frequency and its Relationship with Grade, Stage in Patients with Non Metatstatic Transitional Cell Carcinoma and Disease Free Survival. In this retrospective cohort study, paraffin-embedded specimens from 50 patients with non-metastatic bladder transitional cell carcinoma, referred to Omid hospital from 2003 to 2007, were examined immunohistochemically for HER-2/neu over-expression. The specimens were also reviewed for tumor grade. The patients with superficial tumors underwent TURBT and a full course of intravesical BCG therapy and cases with muscle invasive tumor received cisplatin based chemoradiation. There were 27 [54%] high grade and 23 low grade tumors. The specimens stained for HER-2 over-expression as follow 11 as Zero, 11 as 1+, 13 as 2+ and 15 as 3+. The T stages of Tis, T1, T2 and T3 were detected in 14, 19, 10, and 7 cases respectively. The frequency of strong positive HER-2 tumors [3+] was significantly higher among patients with muscle invasive tumors compared to those with superficial lesions [58.8% vs. 15.2%, p<0.001]. There was also a relatively significant association between strong positive HER-2 expression and high grade tumors [43.5% vs. 18.5% p= 0.055]. The Median follow up time was 14 months [range, 4-52 months] during which 17 cases [34%] experienced recurrence [12 local, 3 bones and 2 lungs]. For all patients 3-year DFS was 62.7% +/- 7.4% which was significantly better for cases with superficial tumors than patients with muscle invasive tumors [78.1% vs. 19.5%, p=0.005]. In patients with strong positive HER-2 expression tumors, DFS was significantly lower compared to the other cases [3-year DFS 19.4% vs. 80%, p<0.001]. No significant difference in DFS was found between high grade and low grade tumors [3-DFS 53.9% vs. 70%, p=0.20]. In This study, strong HER-2 over-expression [3+] was significantly associated with higher T stages as well as high grade tumors. In addition to T stage, strong HER-2 over-expression was a significant predictor of lower disease free survival