Abstract
Conventional renal cell carcinomas (CRCCs) were investigated for the expression of annexin II (ANX II) to determine out whether this calcium-binding protein could serve as a useful prognostic marker. CRCCs and adjacent nonneoplastic tissue from 33 patients were investigated for ANX II by immunohistochemistry, RT-PCR, and western blot analysis. ANX II expression was correlated with tumor differentiation (Fuhrman grade) and to clinical outcome. Tumors were composed of ANX II positive and negative cells. In grade I tumors only a weak membranous staining was seen in immunopositive cells. In grade II and III tumors, however, ANX II was seen in the cytoplasm and at the cell membranes of tumor cells. On serial sections membranous and cytoplasmic immunoreactivity for ANX II occurred predominantly in eosinophilic cells whereas clear cells were mostly immunonegative. The ANX II expression in CRCCs was correlated with clinical outcome and Fuhrman grade. Since ANX II expression is correlated with Fuhrman grade and clinical outcome it may be a useful marker for prognosis in CRCC.
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References
Bander NH (1987) Monoclonal antibodies in urologic oncology. Cancer 60:658–667
Cheng YS, Chen LB (1981) Detection of phosphotyrosine-containing 34,000-dalton protein in the framework of cells transformed with Rous sarcoma virus. Proc Natl Acad Sci U S A 78:2388–2392
Chiang Y, Rizzino A, Sibenaller ZA, Wold MS, Vishwanatha JK (1999) Specific down-regulation of annexin II expression in human cells interferes with cell proliferation. Mol Cell Biochem 199:139–147
Cohen C, McCue PA, Derose PB (1988) Histiogenesis of renal cell carcinoma and renal oncocytoma. An immunohistochemical study. Cancer 62:1946–1951
DeKernion JB, Ramming KP, Smith RB (1978) The natural history of metastatic renal cell carcinomas: a computer analysis. J Urol 120:148–152
Dreier R, Schmid KW, Gerke V, Riehemann K (1998) Differential expression of annexins I, II and IV in human tissues: an immunohistochemical study. Histochem Cell Biol 110:137–148
Droz D, Zachar D, Charbit L, Gogusev J, Chretien Y, Iris L (1990) Expression of the human nephrone differentiation molecules in renal cell carcinomas. Am J Pathol 137:895–905
Eker R, Nesland JM, Andersen A, Johannessen JV (1986) Prognostic factors in renal cell carcinoma. Histol Histopathol 1:255–270
Emoto K, Sawada H, Yamada Y, Fujimoto H, Takahama Y, Ueno M, Takayama T, Uchida H, Kamada K, Naito A Hirao S, Nakajima Y (2001) Annexin II overexpression is correlated with poor prognosis in human gastric carcinoma. Anticancer Res 21:1339–1345
Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6:655–663
Gerke V, Moss SE (1997) Annexins and membrane dynamics. Biochim Biophys Acta 1357:129–154
Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82:331–371
Grone HJ, Weber K, Helmchen U Osborn M (1986) Villin—a marker of brush border differentiation and cellular origin in human renal cell carcinoma. Am J Pathol 124:294–302
Hawkins TE, Merrifield CJ, Moss SE (2000) Calcium signaling and annexins. Cell Biochem Biophys 33:275–296
Kanamaru H, Muranaka K, Mori H, Akino H, Arai Y, Okada K (1996) Analysis of histological heterogeneity in renal cell carcinoma: tumor size-related histological change and its prognostic significance. Int J Urol 3:256–260
Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Storkel S, van den Berg E, Zbar B (1997) The Heidelberg classification of renal cell tumours. J Pathol 183:131–133
Kradjian RM, Bennington JL (1965) Renal carcinoma recurrent 31 years after nephrectomy. Arch Surg 90:192–195
Landis SH, Murray T, Bolden S, Wingo PA (1999) Cancer statistics, 1999. CA Cancer J Clin 49:8–31
Markovic-Lipkovski J, Brasanac D, Todorovic V, Müller CA, Müller GA (1995) Immunomorphological characteristics of renal cell carcinoma. Histol Histopathol 10:651–659
Medeiros LJ, Gelb AB, Weiss LM (1988) Renal cell carcinoma: prognostic significance of morphologic parameters in 121 cases. Cancer 61:1639–1651
Murphy GP, Mostofi FK (1965) The significance of cytoplasmic granularity in the prognosis of renal cell carcinoma. J Urol 94:48–54
Myers GH Jr, Fehrenbaker LG, Kelalis PP (1968) Prognostic significance of renal vein invasion by hypernephroma. J Urol 100:420–423
Nygaard SJ, Haugland HK, Kristoffersen EK, Lund-Johansen M, Laerum OD, Tysnes OB (1998) Expression of annexin II in glioma cell lines and in brain tumour biopsies. J Neurooncol 38:11–18
Oosterwijk E, Rutter DJ, Wakka JC (1986) Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol 123:301–309
Petrides PE, Bock S, Bovens J, Hofmann R, Jakse G (1990) Modulation of pro-epidermal growth factor, pro-transforming growth factor alpha and epidermal growth factor receptor gene expression in human renal carcinomas. Cancer Res 50:3934–3939
Reeves SA, Chavez-Kappel C, Davis R, Rosenblum M, Israel MA (1992) Developmental regulation of annexin II (Lipocortin 2) in human brain and expression in high grade glioma. Cancer Res 52:6871–6876
Reis M, Faria V (1988) Renal carcinomas: reevaluation of prognostic factors. Cancer 61:1192–1199
Reuter VE, Gaudin PB (1999) Adult renal tumors. In: Sternberg S (ed) Diagnostic surgical pathology, 3rd edn. Lippincott Williams & Wilkins, Philadelphia
Roseman BJ, Bollen A, Hsu J, Lamborn K, Israel MA (1994) Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 6:561–567
Sawyer ST, Cohen S (1985) Epidermal growth factor stimulates the phosphorylation of the calcium-dependent 35,000-dalton substrate in intact A-431 cells. J Biol Chem 260:8233–8226
Slaton JW, Inoue K, Perrotte P, El-Naggar AK, Swanson DA, Fidler IJ, Dinney CPN (2001) Expression levels of genes that regulate metastasis and angiogenesis correlate with advanced pathological stage of renal cell carcinoma. Am J Pathol 158:735–743
Sobin LH, Wittekind C (ed) (2002) TNM classification of malignant tumours, 6th edn. Wiley, New York
Störkel S, Eble JN, Adlakha K, Amin M, Blute ML, Bostwick DG, Darson M, Delahunt B, Iczkowski K (1997) Classification of renal cell carcinoma. Cancer 80:987–989
Wallace AC, Nairn RC (1972) Renal tubular antigens in kidney tumors. Cancer 29:977–981
Yeatman TJ, Updyke TV, Kaetzel MA, Dedman JR, Nicolson GL (1993) Expression of annexins on the surfaces of non-metastatic and metastatic human and rodent tumor cells. Clin Exp Metastasis 11:37–44
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Zimmermann, U., Woenckhaus, C., Pietschmann, S. et al. Expression of annexin II in conventional renal cell carcinoma is correlated with Fuhrman grade and clinical outcome. Virchows Arch 445, 368–374 (2004). https://doi.org/10.1007/s00428-004-1103-4
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DOI: https://doi.org/10.1007/s00428-004-1103-4