Correlations of proliferation markers, p53 expression and histological findings in colorectal carcinoma.

AIM To investigate the expression of PCNA, Ki-67 and p53 antibodies in colorectal carcinomas and to establish the relationship between these markers and some particular histological findings of colorectal carcinomas. MATERIAL AND METHODS We determined immunohistochemically the expression of PCNA, Ki-67 and p53 antibodies in 41 cases of colorectal carcinomas. RESULTS In adenocarcinomas, the tumor proliferative activity, detected with PCNA and Ki-67 antibodies, increased with the histological grade. Mucinous adenocarcinomas had a mean PCNA LI of 50% and a mean Ki-67 LI of 32%, while signet ring carcinomas had a mean PCNA LI of 70% and a mean Ki-67 LI of 45%. The proliferative activity in the foci of squamous metaplasia was lower than the proliferative activity of malignant areas in the analyzed adenocarcinomas. The p53 overexpression was detected in 24 cases (58.53%). In adenocarcinomas, the p53 positive rate increased with the dedifferentiation of these tumours. Only 16.66% of the cases of carcinomas with mucus secreting cells overexpressed p53, while adenocarcinomas overexpressed this protein in many more cases (65.71% of the cases). The overexpression of p53 was associated with the highest PCNA and Ki-67 LI. CONCLUSIONS The foci of squamous metaplasia, present in colorectal adeno-carcinomas, do not seem to influence the increase of the tumours. The p53 overexpression was associated with non mucinos colorectal carcinomas and with the histological grade of colorectal adenocarcinomas. The p53 over expression tended to be more frequent in colorectal carcinomas with high proliferative activity.

[1]  P. Garcia,et al.  Prognostic markers for colorectal cancer: Expression of P53 and BCL2 , 1997, World Journal of Surgery.

[2]  M. Banerjee,et al.  Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia , 1999, Pathology & Oncology Research.

[3]  R. Broll,et al.  High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma , 2004, Journal of Cancer Research and Clinical Oncology.

[4]  石田 秀樹.  Proliferative, infiltrative, and metastatic activities in colorectal tumors assessed by MIB-1 antibody , 2004 .

[5]  S. Duffy,et al.  The differential expression of oestrogen receptors, progesterone receptors, Bcl‐2 and Ki67 in endometrial polyps , 2003, BJOG : an international journal of obstetrics and gynaecology.

[6]  S. Cascinu,et al.  Prognostic molecular markers for planning adjuvant chemotherapy trials in Dukes' B colorectal cancer patients: how much evidence is enough? , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  R. Broll,et al.  Colorectal carcinomas with high MIB‐1 labelling indices but low pKi67 mRNA levels correlate with better prognostic outcome , 2003, Histopathology.

[8]  M. Zabel,et al.  Prognostic significance of metallothionein expression in correlation with Ki-67 expression in adenocarcinomas of large intestine. , 2003, Histology and histopathology.

[9]  S. Torp,et al.  Comparison of Ki-67 equivalent antibodies. , 2002, Journal of clinical pathology.

[10]  K. Gatter,et al.  Ki67 protein: the immaculate deception? , 2002, Histopathology.

[11]  R. Houlston,et al.  What we could do now: molecular pathology of colorectal cancer , 2001, Molecular pathology : MP.

[12]  J. Papadimitriou,et al.  Computerized image analysis of p53 and proliferating cell nuclear antigen expression in benign, hyperplastic, and malignant endometrium. , 2001, Archives of pathology & laboratory medicine.

[13]  T. Ince,et al.  Surrogate Biomarkers of HPV Infection in Cervical Neoplasia Screening and Diagnosis , 2001, Advances in anatomic pathology.

[14]  M. Banerjee,et al.  Immunohistochemical Expression of bcl-2 and p53 Oncoproteins: Correlation with Ki67 Proliferation Index and Prognostic Histopathologic Parameters in Colorectal Neoplasia , 2000, Applied immunohistochemistry & molecular morphology : AIMM.

[15]  N. Kohno,et al.  Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer. , 2000, International journal of oncology.

[16]  Stanley R. Hamilton,et al.  Pathology and genetics of tumours of the digestive system , 2000 .

[17]  Parfrey,et al.  bcl‐2 protein expression is associated with better prognosis in colorectal cancer , 1999, Histopathology.

[18]  R. Palmqvist,et al.  Low tumour cell proliferation at the invasive margin is associated with a poor prognosis in Dukes' stage B colorectal cancers , 1999, British Journal of Cancer.

[19]  Zhang Hong.  Evaluation of four antibodies in detecting p53 protein for predicting clinicopathological and prognostic significance in colorectal adenocarcinoma. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[20]  J. Bernheim,et al.  Proliferating cell nuclear antigen as a marker of cell kinetics in aberrant crypt foci, hyperplastic polyps, adenomas, and adenocarcinomas of the human colon. , 1997, American journal of surgery.

[21]  M. Cybulski,et al.  [P53 protein in adenocarcinoma of the large intestine]. , 1997, Wiadomosci lekarskie.

[22]  S. Kagawa,et al.  [Evaluation of Ki67 antigen using MIB1 antibody as a prognostic factor in renal pelvic and ureteral cancer]. , 1996, Nihon Hinyokika Gakkai zasshi. The japanese journal of urology.

[23]  H. Yamagiwa,et al.  [Immunohistochemical study of PCNA, EGFR, c-erbB-2 and p53 in carcinomas of large intestine]. , 1995, Rinsho byori. The Japanese journal of clinical pathology.

[24]  Y. Takano,et al.  [Analyses of PCNA and AgNOR on advanced colorectal cancer as predictive indicators of the prognosis]. , 1994, Nihon Geka Gakkai zasshi.

[25]  U. Löhrs,et al.  Comparison of different monoclonal antibodies for the immunohistochemical assessment of cell proliferation in routine colorectal biopsy specimens. , 1994, Scandinavian journal of gastroenterology.

[26]  Johannes Gerdes,et al.  Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections , 1992, The Journal of pathology.

[27]  J. Gerdes,et al.  Identification of proliferating cells by Ki-67 antibody. , 1990, Methods in cell biology.

[28]  F. Borchard,et al.  Assessment of cell proliferation in colorectal carcinomas using the monoclonal antibody KI‐67. Correlation with pathohistologic criteria and influence of irradiation , 1989, Cancer.

[29]  R. Bravo,et al.  Changes in the nuclear distribution of cyclin (PCNA) but not its synthesis depend on DNA replication. , 1985, The EMBO journal.