Holmäng S, Andius P, Hedelin H, Wester K, Busch C, Johansson S L
Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden.
J Urol. 2001 Apr;165(4):1124-8; discussion 1128-30.
We studied 363 patients with stage Ta bladder tumors during long-term followup who were classified according to the 1998 WHO and International Society of Urological Pathology consensus classifications. We determine whether various immunohistochemical and molecular markers could predict tumor progression.
A total of 680 patients in western Sweden with a first diagnosis of bladder carcinoma in 1987 and 1988 were registered and followed for at least 5 years. There were 363 (53%) tumors that were papillary stage pTa. The tumors were classified as papillary urothelial neoplasm of low malignant potential in 95 patients, low grade papillary urothelial carcinoma in 160 and high grade carcinoma in 108. Of the patients in the latter group 95 were subdivided into WHO grade 2 and 13 into WHO grade 3. Tissue from the primary tumors that progressed in stage during followup was further analyzed with immunohistochemical methods (p21, p53, Ki67 and pRb), DNA ploidy and mitotic frequency. The results were compared with those in matched controls (nonprogressors).
Recurrence developed in 35% of patients with papillary urothelial neoplasm of low malignant potential compared to 71% with low grade urothelial carcinoma and 73% with high grade carcinoma (p <0.0001). No papillary urothelial neoplasm of low malignant potential progressed in stage. Disease progressed in 4% of patients with low grade compared to 23% with high grade carcinoma (p <0.0001). Of the patients with WHO grade 3 disease progressed in 45% compared to grade 2 in 20% (p <0.0011). At first diagnosis p53 score was significantly higher (p <0.0022) among patients with WHO grade 2 carcinoma which later progressed compared to that in matched controls but there was no significant difference regarding the other markers. In contrast to grade 2 most grade 3 carcinoma was aneuploid, had high mitosis frequency, high p53 and Ki67 scores as well as loss of retinoblastoma gene expression.
The 1988 WHO and International Society of Urological Pathology consensus classifications divide noninvasive papillary bladder tumors into 3 subgroups with different clinical behavior, which seems to be an advantage compared with the 1973 WHO classification. A disadvantage is that the high grade carcinoma group contains 2 subgroups with different progression rates and immunohistochemical marker profiles, corresponding to the 1999 WHO grades 2 and 3. Grade 2 tumors in patients that progressed in stage years later seem to have different immunohistochemical and molecular marker profiles compared to those in matched controls.
我们对363例Ta期膀胱肿瘤患者进行了长期随访研究，这些患者根据1998年世界卫生组织（WHO）和国际泌尿病理学会的共识分类进行了分类。我们确定各种免疫组化和分子标志物是否能够预测肿瘤进展。
瑞典西部共有680例于1987年和1988年首次诊断为膀胱癌的患者被登记并随访至少5年。其中363例（53%）肿瘤为乳头状pTa期。这些肿瘤在95例患者中被分类为低恶性潜能乳头状尿路上皮肿瘤，160例为低级别乳头状尿路上皮癌，108例为高级别癌。后一组患者中95例被分为WHO 2级，13例被分为WHO 3级。对随访期间分期进展的原发性肿瘤组织进一步采用免疫组化方法（p21、p53、Ki67和pRb）、DNA倍体和有丝分裂频率进行分析。将结果与配对对照（未进展者）进行比较。
低恶性潜能乳头状尿路上皮肿瘤患者的复发率为35%，而低级别尿路上皮癌患者为71%，高级别癌患者为73%（p<0.0001）。低恶性潜能乳头状尿路上皮肿瘤无分期进展。低级别患者疾病进展率为4%，而高级别癌患者为23%（p<0.0001）。WHO 3级患者中疾病进展率为45%，而2级患者为20%（p<0.0011）。初次诊断时，后来分期进展的WHO 2级癌患者的p53评分显著高于（p<0.0022）配对对照，但其他标志物无显著差异。与2级相反，大多数3级癌为非整倍体，有丝分裂频率高，p53和Ki67评分高，且视网膜母细胞瘤基因表达缺失。
1988年WHO和国际泌尿病理学会的共识分类将非侵袭性乳头状膀胱肿瘤分为3个具有不同临床行为的亚组，与1973年WHO分类相比这似乎是一个优势。一个缺点是高级别癌组包含2个具有不同进展率和免疫组化标志物谱的亚组，分别对应1999年WHO 2级和3级。数年后分期进展的患者中的2级肿瘤与配对对照相比似乎具有不同的免疫组化和分子标志物谱。
