Abstract
Overexpression of p53 anderbB-2 was studied by immunohistochemistry in formalin-fixed tissue samples of 179 patients with transitional cell carcinoma of the urinary bladder. p53 immunostaining was strongly correlated with tumour stage (P<0.0001). This was driven by a marked difference in p53 expression between pTa (37% positive) and pT1 (71%) tumours, while there was no difference between pT1 and pT2-4 tumours. Similarly, a strong overall association between p53 expression and grade (P<0.0001) was driven by a marked difference between grade 1 (28%) and grade 2 tumours (71%), and there was no significant difference between grade 2 and grade 3 tumours. Surprisingly, the frequency oferbB-2 overexpression was higher in pT1 tumours (74%) than in either pTa (49%;P=0.0265) or pT2-T4 (56%;P=0.0645) tumours. Both p53 anderbB-2 expression was also associated with metastasis. Metastases were found in 77% of patients with p53 positive primary tumours, but in only 50% of the patients with p53 negative primary tumours (P=0.022). Metastases were found in 66% of patients witherbB-2 positive primaries, but in only 37% of theerbB-2 negative primaries (P=0.020). Of 32 patients with positivity for both p53 anderbB-2, 84% developed metastases, as compared to 49% of patients with positivity for either one or neither positive (P=0.002). We conclude that both p53 anderbB-2 over-expression are associated with early invasion in bladder cancer. Furthermore, p53 anderbB-2 may be important predictors for metastasis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abel P, Hall R, Williams G (1988) Should pT1 transitional cell cancers of the bladder still be classified superficial? Br J Urol 62:235–239
Asamoto M, Hasegawa R, Masuko T, Hashimoto Y, Ueda K, Ohtaguro K, Sasaki S, Washida H, Fukushima S (1990) Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. Acta Pathol Jpn 40:322–326
Bartek J, Iggo R, Gannon J, Lane DP (1990) Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene 5:893–899
Bodner S, Minna J, Jensen S, D'Amico D, Carbone D, Mitsudomi T, Fedorko J, Buchhagen D, Nau M, Gazdar A, Linnoila R (1992) Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. Oncogene 743–749
Coombs LM, Pigott DA, Sweeney E, Proctor AJ, Eydmann ME, Parkinson C, Knowles MA (1991) Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br J Cancer 63:601–608
Cunningham J, Lust J, Schaid D, Bren G, Carpenter H, Rizza E, Kovach J, Thibodeau S (1992) Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res 52:1974–1980
Dalbagni G, Presti J, Reuter V, Fair W, Cordon-Cardo C (1992) p53 and chromosome 17 abnormalities in bladder cancer. Proc Am Assoc Cancer Res 32:373
Davidoff AM, Herndon J, Glover NS, Kerns BJ, Pence JC, Iglehart JD, Marks JR (1991) Relation between p53 overexpression and established prognostic factors in breast cancer. Surgery 110:259–264
Flamm J, Havelec L (1990) Factors affecting survival in primary superficial bladder cancer. Eur Urol 17:113–118
Fujimoto K, Yamada Y, Okajima E, Kakizoe T, Sasaki H, Sugimura T, Terada M (1992) Frequent association of p53 gene mutation in invasive bladder cancer. Cancer Res 52:1393–1398
Hsu S, Raine M, Fanger H (1981) Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: a comparison study between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Hsuan JJ, Panayotou G, Waterfield MD (1989) Structural basis for epidermal growth factor receptor function. Prog Growth Factor Res 1:23–32
Iggo R, Gatter K, Bartek J, Lane D, Harris A (1990) Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet 335:675–679
Isola J, Visakorpi T, Holli K, Kallioniemi OP (1992) Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst 84:1109–1114
Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 49:650–655
Kim JH, Takahashi T, Chiba I, Park JG, Birrer MJ, Roh JK, De LH, Kim JP, Minna JD, Gazdar AF (1991) Occurrence of p53 gene abnormalities in gastric carcinoma tumors and cell lines. J Natl Cancer Inst 83:938–943
Lane D (1992) p53, guardian of the genome. Nature 358:15–16
Levine AJ (1989) The p53 tumor suppressor gene and gene product. Int Symp Princess Takamatsu Cancer Res Fund 20:221–230
Marks J, Davidoff A, Kerns B, Humphrey P, Pence J, Dodge R, Clarke-Pearson D, Iglehart J, Bast RJ, Berchuck A (1991) Over-expression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51:2979–2984
McCann A, Dervan PA, Johnston PA, Gullick WJ, Carney DN (1990) c-erbB-2 oncoprotein expression in primary human tumors. Cancer 65:88–92
McCann AH, Dervan PA, O'Regan M, Codd MB, Gullick WJ, Tobin BM, Carney DN (1991) Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer. Cancer Res 51:3296–3303
Moriyama M, Akiyama T, Yamamoto T, Kawamoto T, Kato T, Sato K, Watanuki T, Hikage T, Katsuta N, Mori S (1991) Expression of c-erbB-2 gene product in urinary bladder cancer. J Urol 145:423–427
Morkve O, Laerum OD (1991) Flow cytometric measurement of p53 protein expression and DNA content in paraffin-embedded tissue from bronchial carcinomas. Cytometry 12:438–444
Mostofi F (1973) Histological typing of urinary bladder tumors. World Health Organization, Geneva
Olumi AF, Tsai YC, Nichols PW, Skinner DG, Cain DR, Bender LI, Jones PA (1990) Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder. Cancer Res 50:7081–7083
Omori K (1991) DNA content and c-erbB-2 oncoprotein expression in hepatic metastases from colorectal carcinoma in relation to clincopathologic findings and prognosis. Nippon Geka Gakkai Zasshi 92:1469–1479
Presti J, Reuter V, Galan T, Fair W, Cordon-Cardo C (1991) Suppressor gene loss in human bladder cancer. Cancer Res 51:5405–5409
Raghavan D, Shipley W, Garnick M, Russel P, Richie J (1990) Biology and management of bladder cancer. N Engl J Med 322:1129–1138
Sarkis AS, Dalbagni G, Cordon CC, Zhang ZF, Sheinfeld J, Fair WR, Herr HW, Reuter VE (1993) Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J Natl Cancer Inst 85:53–59
Scott N, Sagar P, Stewart J, Blair GE, Dixon MF, Quirke P (1991) p53 in colorectal cancer: clinicopathological correlation and prognostic significance. Br J Cancer 63:317–319
Serio G (1991) c-erbB-2 gene product-like expression in urothelial carcinomas of the human bladder. Its value as a prognostic indicator in superficial tumors. Pathologica 83:413–420
Sidransky D, Von EA, Tsai YC, Jones P, Summerhayes I, Marshall F, Paul M, Green P, Hamilton SR, Frost P et al. (1991) Identification of p53 gene mutations in bladder cancers and urine samples. Science 252:706–709
Somerville JE, Clarke LA, Biggart JD (1992) c-erbB-2 overexpression and histological type of in situ and invasive breast carcinoma. J Clin Pathol 45:16–20
Steinmeyer K, Deppert W (1988) DNA binding properties of murine p53. Oncogene 3:501–507
Stenman G, Sandros J, Nordkvist A, Mark J, Sahlin P (1991) Expression of the ERBB2 protein in benign and malignant salivary gland tumors. Genes Chromosom Cancer 3:128–135
Tribukait B (1987) Flow cytometry in assessing the clinical aggressiveness of genito-urinary neoplasms. World J Urol 5:108–122
Tsai Y, Nichols P, Hiti A, Williams Z, Skinner D, Jones P (1990) Allelic losses of chromosomes 9, 11 and 17 in human bladder cancer. Cancer Res 50:44–47
Ueda M (1992) New prognostic factors in patients with esophageal squamous carcinoma. Gan To Kagaku Ryoho 19:20–25
UICC (1978) TNM classification of malignant tumours. International Union against Cancer, Geneva
Visakorpi T, Kallioniemi OP, Heikkinen A, Koivula T, Isola J (1992) Small subgroup of aggressive, highly proliferative prostatic carcinomas defined by p53 accumulation. J Natl Cancer Inst 84:883–887
Weinberg R (1991) Tumor suppressor genes. Science 254:1138–1146
Wood DJ, Wartinger DD, Reuter V, Cordon-Cardo C, Fair WR, Chaganti RS (1991) DNA, RNA and immunohistochemical characterization of the HER-2/neu oncogene in transitonal cell carcinoma of the bladder. J Urol 146:1398–1401
Wright C, Mellon K, Johnston P, Lane DP, Harris AL, Horne CH, Neal DE (1991) Expression of mutant p53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br J Cancer 63:967–970
Yonemura Y, Ninomiya I, Ohoyama S, Kimura H, Yamaguchi A, Fushida S, Kosaka T, Miwa K, Miyazaki I, Endou Y (1991) Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma. Cancer 67:2914–2918
Zhau HE, Zhang X, Von EA, Scorsone K, Babaian RJ, Ro JY, Hung MC (1990) Amplification and expression of the c-erbB-2/neu proto-oncogene in human bladder cancer. Mol Carcinog 3:254–257
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moch, H., Sauter, G., Moore, D. et al. p53 anderbB-2 protein overexpression are associated with early invasion and metastasis in bladder cancer. Vichows Archiv A Pathol Anat 423, 329–334 (1993). https://doi.org/10.1007/BF01607144
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01607144