DNA Ploidy Study in 1,673 Fresh Solid Tumors / 대한암학회지

PURPOSE: To evaluate the possible role of DNA content abnomrality in solid tumors as a diagnostic indicator in Korean patients, the incidence of aneuploidy in the major organs were analyzed and compared with the incidences which have been reported in the literatures. MATERIALS AND METHODS: Flow cytometric analysis of DNA content were performed on the 1673 fresh tissues of neoplastic lesions which were obtained for the last five years in Hospital. RESULTS: The frequency of aneuploidy was more than 50% in the primary malignant tumors of the stomach, colon, esophagus, liver, biliary tract, pancreas, head and neck organs, salivary gland, lung, breast, ovary, CNS and urinary tract. However, the frequency of aneuploidy was as low as 7% in papillary carcinoma of thyroid and about 30% in renal cell carcinoma and malignant lymphomas. High frequency of aneuploidy (more than 70%) was seen in the metastatic tumors in liver, brain, ovary and lymph nodes. Aneuploidy was also found in benign tumors of salivary gland, adenomas of endocrine organs, meningiomas, smooth muscle tumors and schwannomas. CONCLUSION: The results of present study were in concordant with those of the other domestic and foreign studies. Although aneuploidy can be observed in some benign tumors, DNA ploidy pattern is considered to be an important diagnostic and prognostic factors in malignant lesions of the various organs.

Immunohistochemical Demonstration of C-erbB-2 Oncoprotein Expression in Transitional Cell Carcinoma of the Bladder: Correlative Study with Tumor Grade, Stage, Proliferating Cell Nuclear Antigen Expression, Nucleolar Organizer Regions Per Nucleus, and Flow / 대한비뇨기과학회지

C-erbB-2 oncoprotein has been known to act as growth factor receptor responsible for the regulation of cellular growth, proliferation and differentiation and has been demonstrated in a number of cancers by immunohistochemical as well as matrix blotting techniques. Breast and ovarian cancer patients, whose tumor cells have amplification or overexpression of this oncoprotein, have been suggested to have worse prognosis. Yet, there are only a few studies on c-erbB-2 oncoprotein expression in transitional cell carcinoma(TCC) of the bladder. The aim of this study was to examine c-erbB-2 oncoprotein expression in bladder cancer to assess its potential as a useful prognostic marker in transitional cell carcinoma of the bladder. Deparaffinized tumor specimens from 42 patients with TCC of the bladder and 3 normal bladder tissue specimens were utilized. C-erbB-2 oncoprotein expression was detected by immunohistochemical analysis and then correlated with conventional prognostic variables such as histologic tumor grade, stage and DNA ploidy. In addition, we related the expression of c-erbB-2 oncoprotein to indicators of cellular proliferative activities such as proliferating cell nuclear antigen(PCNA), mean number of silver nucleolar organizer regions(AgNORs) per nucleus, flow cytometric S-phase fraction(CPF) and proliferation index(PI). The incidence of c-erbB-2 oncoprotein expression in Ash grade IV TCC of bladder was higher than that in Ash grade II and III (Chi-square test, p<0.05). The incidence of positive immunoreaction was higher in cases with muscle invasion and metastasis than in superficial tumors with statistical significance(p<0.05). In addition, statistical significant correlation was noted between c-erbB-2 oncoprotein expression and PCNA expression rate. But there were no significant differences in c-erbB-2 oncoprotein expression to DNA ploidy, PI nor SPF by flow cytometry and mean number of AgNORs per nucleus. The results of this study suggests that the c-erbB-2 oncoprotein together with other predictive parameters may serve to provide a phenotypic profile which permits more accurate forecasting of bladder cancer behavior and may prove to be useful in the future as an important guide to specific anti-tumor therapy.

Clinical significance of silver binding nucleolar organizer regions(AgNORs) in transitional cell carcinoma of the bladder : The correlative study with flow cytometric SPF, PI and PCNA / 대한비뇨기과학회지

Nucleolar organizer regions(NORs) contain coding genes for ribosomal RNA and contribute the regulation of cellular protein synthesis. AgNORs numbers correlate with growth fraction and have been reported the AgNORs counts may have a diagnostic and prognostic utility in other human tumors. We investigated the diagnostic usefulness of AgNORs staining technique as a discriminant for malignancy and assessed the value as a potential method for the estimation of cell kinetics. In addition. we compared the AgNOR counts with flow cytometric analysis of ploidy, S-phase fraction, proliferation index, and PCNA expression rate. There was a statistically significant difference of AgNORs counts between superficial bladder tumor and invasive bladder tumor. But there was no relationship between the mean number of AgNORs per nucleus and histological grade. DNA aneuploid group was associated with higher AgNORs counts than diploid group, but the difference was statistically insignificant. The mean number of AgNORs per nucleus had significant relationship to SPF(r=0.43, p<0.05) and PI(r=0.41, p<0.05.) We concluded that this method alone does not offer a reliable histological discriminant for malignancy. Further studies are needed to confirm that AgNORs counting is a useful method for evaluating the proliferative activity and this technique may serve as a prognostic factor additional to the current histopathological grading criteria of the bladder cancer.

An immunohistochemical demonstration of C-erbB-2 oncoprotein expression in prostatic adenocarcinoma / 대한비뇨기과학회지

The c-erbB-2 gene is located on q21 of chromosome 17. The c-erbB-2 oncoprotein exhibits tyrosine kinase activity, appears to be a receptor for to yet unidentified growth factor and has been demonstrated in a number of cancers by immunohistochemical as well as matrix blotting techniques. Breast and ovarian cancer patients, whose tumor cells have amplification or overexpression or this oncoprotein, have been suggested to have worse prognosis. But there were only a few reports on c-erbB-2 oncoprotein expression in prostatic carcinoma. The aim of this study was to ex- amine the c-erbB-2 oncoprotein expression in pnstatic adenocarcinoma to assess its potential as a useful prognostic marker in this disease. The samples were considered immunoreactive when distinct cell membrane was slained. These staining pattern was noted exclusively in neoplastic cells and was unirormly distributed throughout the neoplastic cell population. Incidence of c-erbB-2 oncoprotein expression in Gleason grade 4 and 5 prostatic adenocarcinoma is significantly higher than that in Gleason grade 1, 2 and 3(Chi-square test, p<0.05), and incidence in stage D prostatic adenocarcinoma is significantly higher than that in stage A, B and C(Chi-square test, p<0.25). But there is no significant difference of c-erbB-2 oncoprotein expression according to DNA ploidy or proliferation index by flow cytometry. High proliferating cell nuclear antigen(PCNA) expression rate is not associated with c-erbB-2 oncoprotein expression. The results of this study suggest that the c-erbB-2 oncoprotein together with other predictive parameters may serve to provide a phenotypic profile which permits more accurate forecasting of prostatic cancer behavior, and may prove useful in the future as an important guide for directing speciric anti-tumor therapy. To investigate these possibilities, further studies based on larger numbers or cases with complete follow up data will be needed.

Prognostic significance of silver-binding nucleolar organizer regions(AgNORs) in prostatic carcinoma: The correlative study with flow cytometric S-phase fraction, proliferation inde and proliferating cell nuclear antigen(PCNA) expression rate / 대한비뇨기과학회지

The nucleolus plays a vital role in control of cell proliferation and protein synthesis. Nucleolar organizer regions (NORs), segment of DNA closely associated with nucleoli, contain coding genes for ribosomal RNA and contribute the regulation of cellular protein synthesis. Detectable by the argyrophilia of associated proteins, silver-binding nucleolar organizer regions (AgNORs) numbers correlate with growth fraction and have been reported the AgNORs counts may have diagnostic and prognostic utility in other human tumors. We investigated further the diagnostic usefulness of the AgNORs technique as a discriminant for malignancy. In addition, we compared the AgNORs counts with flow cytometric analysis of ploidy, S-phase fraction (SPF), proliferation index (PI), and proliferating cell nuclear antigen (PCNA) expression rate. Also, we assessed this technique as a possible prognostic indicator for prostatic carcinoma. There was no linear relationship between the mean number of AgNORs per nucleus versus Gleason histologic grade (r=0.093, p=0.578) and DNA aneuploid group was associated with higher AgNORs counts than diploid group in clinical stage C and D, but the differences were statistically insignificant. The mean number of AgNORs per nucleus had no significant relationship to SPF (r=-0.09, p=0.58) and PI (r=-0.119, p=0.477). Also, there was no significant relationship between mean number of AgNORs and PCNA (r= 0.205, p=0.217). We evaluated the probability, of survival for 29 patients with close follow-up. There was no significant difference of survival between high and low AgNORs number group, even after combined stratification by Gleason grade (Kaplan-Meier analysis with generalized Wil-coxon test). We conclude that this method alone does not offer a reliable histologic discriminanl for malignancy in prostatic tumor, and it is concluded that this technique is of no value in predicting prognosis for prostatic carcinoma.

The clinical significance of expression of proliferating cell nuclear antigen(PCNA) in prostatic carcinoma: the correlative study with glandular differentiation and flow cytometric DNA analysis / 대한비뇨기과학회지

The expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically in I8 patients with benign glandular hyperplasia (BPH) and 40 patients with prostatic carcinoma with anti-PCNA, cyclin monoclonal antibody. using routinely processed tissue sections without interfering with histopathological diagnosis. The PCNA expression rates were compared with flow cytometric DNA analysis in 29 patients and Gleason histologic grade in 40 patients with prostatic carcinoma. In BPH tissues basal cells show positivities for PCNA and secretory cells show essential positive reaction with anti-PCNA/cyclin monoclonal antibody. In prostatic carcinoma the PCNA expression rate ranged from 3.70% to 48. 53% (mean value 22.36%1. Prostatic carcinoma with Gleason grade 5 showed the highest PCNA expression rate (mean value 32.22%) and carcinoma with Gleason grade l showed the lowest PCNA expression rate (mean value 3.TS%). There were statistically significant differences of PCNA expression rate according to Gleason grades (p=0.001. Kruskal-Wallis test). When DNA ploidy was analyzed to assess the relationship to other tumor variables DNA aneuploid group was associated with higher Gleason grade and higher PCNA expression rate than diploid group. but the differences were statistically insignificant. The DNA aneuploid group had higher percentage of S-phase cells (S-phase Fraction) by flow cytometry than diploid group (mean value l3.48 =6 in diploid group and 19.78% in aneuploid group and this difference was statistically significant (p=0.01. Mann-Whitney test). From the above results. it is clear that PCNA expression is useful as an nuclear antigenic marker of cellular proliferation and offers an opportunity for analyzing cell kinetics successfully in prostatic carcinoma. It will be merited as a means to detect prostatic carcinomas with high potential for invasion. metastasis and clinical progression.