Espressione di oncogeni di proliferazione e morte cellulare nel carcinoma superficiale della vescica: Expression of oncogenes in relation to cell proliferation and death in superficial bladder carcinoma
Restricted accessResearch articleFirst published online April, 1995
Espressione di oncogeni di proliferazione e morte cellulare nel carcinoma superficiale della vescica: Expression of oncogenes in relation to cell proliferation and death in superficial bladder carcinoma
Although superficial bladder cancer may be considered “benign”, it is still today a many-sided neoplasm with a prognosis that cannot be well-defined with known traditional parameters. Proliferation indices Ki67 and AgNOR associated with the expression of some oncogenes (p53, Rb, c-myc, BCL2, c-erbB-2) in relation to traditional parameters could help in the prognosis definition of individual patients. 111 patients with superficial bladder cancer were studied for this purpose, relating the grade, stage, follow-up and morphotype to the proliferation indices. Significant correlations were found with AgNOR, but only for grade with Ki67. The study of the oncoproteins and their different expression showed that those alterations typical of infiltration are already present in the superficial forms, with a significant correlation between oncogenic alterations and grade and stage of disease (p53, Rb) on the one hand, and above all of disease-free interval and progression (c-erbB-2) on the other. Lastly, assessment of the oncoproteins c-myc and BCL2, oncogenes connected with the programmed cell death mechanism (apoptosis), showed important correlations with the neoplastic progression of disease in relation to the p53 expression and proliferative activity.
LeviF., La VecchiaC., RandimbisonL., FranceschiS.: Incidence of infiltrating cancer following superficial bladder carcinoma. Int. J. Cancer, 55: 419–421, 1993.
2.
KiemeneyL.A.L.M., WitjesJ.A., HeijbroekR.P., VerbeekA.L.M., DebruyneF.M.J.: Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer. J. Urol., 150: 60–64, 1993.
3.
Van Der MeijdenA.P.M., KurtH.K., OosterlinkW., SylvesterR.: Prognostic factors in superficial bladder cancer: consequences for therapy and follow-up. Proc. 3rd int. symp. on recent advances in urological cancer diagnosis and treatment. Paris, June 17-19, 1992 (Abstract).
4.
ParmarM.K.B., FreedmanL.S., HargreaveT.B., TolleyD.A.: Prognostic factors for recurrence and follow-up policies in the treatment of superficial bladder cancer: report from the BRMC subgroup on superficial bladder cancer. J. Urol., 142: 284–288, 1989.
5.
SolowayM.: Managing superficial bladder cancer: an overview. Proc. 3rd int. symp. on recent advances in urological cancer diagnosis and treatment. Paris, June 17-19, 1992 (Abstract).
6.
GilbertH.A., LoganJ.L., KaganA.R., FriedmanH.A., CoveJ.K., FoxM., MuldoonT.M., LonniY.W., RoweJ.K.: The natural history of papillary transitional cell carcinoma of the bladder and its treatment in an unselected population on the basis of histologic grading. J. Urol., 119: 488–492, 1978.
7.
FerrarisV.: Recurrences during chemoprophylactic treatment of superficial tumours of the bladder. J. Urol., 136: 576–579, 1986.
LipponenP.K., EskelinenM.J., KivirantaJ., PesonenE.: Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction. J. Urol., 146: 1535–1540, 1991.
10.
HasuiY., OsadaY., KitadaS., NishiS.: Significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer. Urology, 43: 782–786, 1994.
11.
HerrH.W., LaudoneV.P., WithmoreW.F.: An overview of intravesical therapy for superficial bladder tumours. J. Urol., 138: 1363–1368, 1987.
12.
HeneyN.M., AhmedS., FlanaganM.J., FrableW., CorderM.P., HafermanM.D., HawkinsI.R.: Superficial bladder cancer: progression and recurrence. J. Urol., 130: 1083–1086, 1983.
13.
WrightC., MellonK., JohnstonP.: Expression of mutant p-53, c-erbB-2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder. Br. J. Cancer, 63: 967–970, 1991.
14.
FujimotoA., YamadaY., OkajiamaE., KakizoeT., SasakiH., SugimuraT., TeradaM.: Frequent association of p53 gene mutation in invasive bladder cancer. Cancer Res., 52: 1393–1398, 1992.
15.
HabuchiT., OgawaO., KakehiY., OguraK., KoshibaM., SugiyamaT., YoshidaO.: Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. J. Urol., 148: 1595–1599, 1992.
16.
SarkisS.A., DalbagniG., Cordon-CardoC., ZhangZ.F., SheinfeldJ., FairW.R., HerrH.W., ReuterV.E.: Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: a marker for disease progression. J. Natl. Cancer Inst., 85: 53–59, 1993.
17.
MochH., SauterG., MooreD., MihatschM.J., GudatF., WaldmanF.: p53 and erbB-2 protein overexpression are associated with early invasion and metastases in bladder cancer. Virchows Arch. A. Pathol. Anat., 423: 329–334, 1993.
18.
LipponenP.K.: Overexpression of p53 nuclear oncoprotein in transitional cell bladder cancer and its prognostic value. Int. J. Cancer, 60: 266–270, 1993.
19.
ThomasD.J., RobinsonM.C., ChartonR., WilkinsonS., ShentonB.K., NealD.E.: p53 expression ploidy and progression in pT1 transitional cell carcinoma of the bladder. Br. J. Urol., 73: 533–537, 1993.
20.
GardinerR.A., WalshV., AllenS., RahmanM.L.T.H., SamaratungaG.J., LavinS., LavinM.F.: Immunohistological expression of p53 in primary pT1 transitional cell bladder cancer in relation to tumour progression. Br. J. Urol., 73: 526–532, 1994.
21.
HorowitzJ.M., ParkS.H., BogenmannE., ChengJ.C., YendallD.W., KayF.S., MinnaJ.D., PryjaT.P., WeinbergR.A.: Frequent inactivation of the retinoblastoma antioncogene is restricted to a sub-set of human tumour cells. Proc. Nat. Acad. Sci., 87: 2775–2779, 1990.
22.
IshikawaJ., XuH.J., HuS.X., YandellD.W., MaedaS., KamidonoS., BenedictW.F., TakahashiR.: Inactivation of the retinoblastoma gene in human bladder and renal cell-carcinomas. Cancer. Res., 51: 5736–5743, 1991.
23.
PrestiJ.C., ReuterV.E., GalanT., FairW.F., Cordon-CardoC.: Molecular genetic alterations in superficial and locally advanced human bladder cancer. Cancer Res., 51: 5405–5409, 1991.
24.
CairnsP., ProctorA.J., KnowlesM.A.: Loss of heterozygosity at the Rb locus is frequent and correlates with muscle invasion in bladder carcinoma. Oncogene, 6: 2305–2309, 1991.
25.
XuH.J., CairnsP., HuS.X., KnowlesM.A., BenedictW.F.: Loss of Rb protein expression in primary bladder cancer correlates with loss of heterozygosity at the Rb locus and tumour progression. Int. J. Cancer, 53: 781–784, 1993.
Del SennoL., MaestriI., PivaR., HanauS., ReggianiA., RomanoA., RussoG.: Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades. J. Urol., 142: 146–149, 1989.
28.
LipponenP.: Expression of c-erbB-2 oncoprotein in transitional cell bladder cancer. Eur. J. Cancer, 29: 749–753, 1993.
29.
KakizoeT., MatumotoK., NishioY., OhtaniM., KishiK.: Significance of carcinoma in situ and dysplasia in association with bladder cancer. J. Urol., 133: 395–398, 1985.
30.
LipponenP.K., EskelinenM.J., JauhiainenK., HarjuE., TerhoR., HaapasaloH.: Grading of superficial bladder cancer by quantitative mitotic frequency analysis. J. Urol., 149: 36–41, 1993.
LutzeyerW., RubbenH., DahmH.: Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J. Urol., 127: 250–252, 1982.
33.
MostofiF.K., SobinL.H., TorloniH.: Histological typing of urinary bladder tumours. In: International Histological Classification of Tumours.Geneva, WHO n. 10, 1973.
34.
HarmerM.H.: TNM classification of malignant tumours, 3rd. Ed. Geneva, International Union Against Cancer, 1978.
35.
AbelP.D., HendersonD., BennettM.K., HallR.R., WilliamsG.: Differing interpretation by pathologists of the pT category and grade of transitional cell cancer of the bladder. Br. J. Urol., 62: 339–342, 1988.
36.
OomsE.C.M., AndersonW.A.D., AlonsC.L., BoonM.E., ValdhuizenR.W.: Analysis of the performance of pathologists in grading bladder tumours. Hum. Pathol., 14: 140–143, 1983.
37.
GerdesJ., SchwabU., LemkeH., SteinH.: Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int. J. Cancer, 31: 13–20, 1983.
38.
PlotonD., MenagerM., JeannesonP., HimberG., PigeonF., AdnetJ.J.: Improvement in the staining and in the visualization of the argyrophilic proteins of the nucleolar organizer regions at the optical level. Histochem. J., 18: 5–14, 1986.
39.
DerenziniM., PessionA., TrerèD.: Quantity of nucleolar silver stained protein is related to proliferating activity in cancer cells. Lab. Invest., 63: 137140, 1990.
40.
RaymondW.A., LeongA.S.Y.: Nucleolar organizer regions relate to growth fractions in human breast carcinoma. Hum. Pathol., 20: 741–746, 1989.
41.
LeekR.D., AlisonM.R., SarrafC.E.: Variations in the occurrence of silver staining nucleolar organizer regions (AgNORs) in non proliferating and proliferating tissues. J. Pathol., 165: 43–51, 1991.
42.
HittmairA., OfnerD., OffnerF., FeichtingerH., EnsingerC., RogatschH., MikuzG.: In vitro investigations of interphase and metaphase argyrophilic nucleolar organizer regions and cellular proliferation in the human urothelial cancer cell line HOK-1. Virchows Arch. A. Pathol. Anat., 424: 149–154, 1994.
43.
De GaetaniC., RighiE., FerrariG., MigaldiM., CastagnettiG., FerrariP., TrentiniG.P.: Parametri di proliferazione cellulare nel carcinoma della vescica con infezione da HPV. 3 Congr. Naz. Soc. Ital. Urol. Oncol., pp. 88–91, Ed. Forum, Milano, 1993.
44.
LipponenP.K., EskelinenM.J., NordlingS.: Nucleolar organizer regions (AgNORs) as predictors in transitional cell bladder cancer. Br. J. Cancer, 64: 1139–1144, 1991.
45.
LipponenP.K.: Image analysis of AgNOR proteins in transitional cell bladder cancer. J. Pathol., 171: 279–283, 1993.
46.
CairnsP., SuarezV., NewmanJ., CrockerJ.: Nucleolar organizer regions in transitional cell tumours of the bladder. Arch. Pathol. Lab. Med., 113: 1250–1252, 1989.
47.
MansourP., CrockerJ., NewmanJ.: Lack of prognostic value of nucleolar organizer region enumeration in transitional cell carcinoma of the bladder. Arch. Pathol. Lab. Med., 114: 1261, 1990.
48.
HansenA.B., OstergardB.: Nucleolar organizer regions in hyperplastic and neoplastic prostatic tissue. Virchows Arch. A. Pathol. Anat., 417: 9–13, 1990.
49.
BushC., PriceP., NortonJ., ParkinsC.S., BaileyM.J., BoydJ., JonesC.R., A'HernR.P., HorwichA.: Proliferation in human bladder carcinoma measured by Ki67 antibody labelling: its potential clinical importance. Br. J. Cancer, 64: 357–360, 1991.
50.
LipponenP.K., EskelinenM.J.: Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin immunostaining and its prognostic value. Br. J. Cancer, 66: 171–176, 1992.
51.
LimasC., BairR., BernhartP., ReddyP.: Proliferative activity of normal and neoplastic urothelium and its relation to epidermal growth factor and transferrin receptors. J. Clin. Pathol., 46: 810–816, 1993.
52.
CoombsL.M., PigottD.A., SweeneyE., ProctorA.J., EydmannM.E., ParkinsonC., KnowlesM.A.: Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder. Br. J. Cancer, 63: 601–608, 1991.
53.
KihanaT., TsudaH., TeshimaS., NomotoK., TsuganeS., SonodaT., MatsumuraS., HirohashiS.: Prognostic significance of the over-expression of c-erbB-2 protein in adenocarcinoma of the uterine cervix. Cancer, 73: 148–153, 1994.
54.
Cordon-CardoC., DalbagniG., SaezG.T., OlivaM.R., ZangZ.F., RosaiJ., ReuterV.E., PellicerA.: p53 mutations in human bladder cancer: genotypic versus phenotypic patterns. Int. J. Cancer, 56: 347–353, 1994.
55.
RossiE., GaragnaniL., RighiE., FerrariG., De GaetaniC., FerrariP., TrentiniG.P.: Mutazione genica ed espressione di p53 nel carcinoma uroteliale della vescica. 4 Congr. Naz. Soc. Ital. Urol. Oncol., pp. 17–18, Ed. Forum, Milano (Abstract).
56.
LipponenP.K.: Interrelationship between expression of p53, proliferating cell nuclear antigen and c-erbB-2 in bladder cancer. Pathobiology, 61: 178–182, 1993.
57.
Cordon-CardoC., WartingerD., PetrylakD., DalbagniG., FairW.R., FuksZ., ReuterV.E.: Reports: Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J. Nat. Cancer Inst., 84: 1251–1261, 1992.
58.
BissonnetteR.P., EcheverriF., MahboubiA., GreenD.R.: Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature, 359: 552–554, 1992.
59.
FanidiA., HarringtonE.A., EvanG.I.: Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature, 359: 554–556, 1992.
60.
LaneD.: p53, guardian of the genoma. Nature, 358: 15–16, 1992.
