High Proliferating Cell Nuclear Antigen Index Research Articles

Prognostic factors in differentiated thyroid cancer—a 20-year surgical outcome study

AimsThe aim of this study was to determine prognostic factors in patients operated on for well-differentiated thyroid cancer (WDTC).Patients and methodsA retrospective cohort study of patients with WDTC treated at our institution between 1989 and 1991 (n = 97; mean age 52.3 years, 78 females, follow-up 124.6 ± 75.1 months) was made. Multivariate analysis was performed including: age, gender, size of primary tumor, location and number of foci in thyroid tissue, clinical stage, thyroid capsule infiltration, tumor histological type, extent of surgery, prognosis based on the AGES and MACIS scores, and tumor proliferative activity based on determination of proliferating cell nuclear antigen (PCNA) and Ki-67 expression in tumor tissue and nodal metastases.ResultsThe multivariate analysis showed increased relative risk (RR) of death for: age above 60 years (7.39; p < 0.001), pTm (2.94; p = 0.002), pT3 (11.83; p < 0.001), and pN1 (4.11; p < 0.001). Total thyroidectomy decreased RR of death (0.39; p = 0.023) when compared to more limited resections. Moderate and high PCNA index was associated with 48.3% and 87.5% mortality, respectively, while Ki-67 index was associated with the highest mortality rate (76%) in the group of medium values.ConclusionsDespite good prognosis in WDTC, factors that most significantly affect overall survival rate include age, size of primary lesion and multifocal disease, presence of nodal metastases, and extent of primary surgery.

A study of proliferative activity, angiogenesis and nuclear grading in renal cell carcinoma

To evaluate the role of proliferative marker, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) as prognostic markers in renal cell carcinoma (RCC) and to see their relationship with the clinical stage and nuclear grades, we studied 30 cases of RCC for nuclear grading (Fuhrman's nuclear grade), MVD (using anti CD-34 antibody), and PCNA labeling index (using anti-PCNA antibody) over a period of 2.5 years. Staging was assessed by peroperative and radiologic findings. The area of highest MVD within the tumor was selected for microvessel count (MVC) per high-power field (0.1885 mm 2 area). PCNA labeling index was determined by counting percentage of positively stained tumor cell nuclei. PCNA labeling index above 60% was taken as high PCNA index and up to 60% was considered low. There was significant positive correlation between PCNA labeling index with both nuclear grade and clinical stage using Spearman's correlation coefficient. No association was noted between MVC with PCNA, nuclear grade, and clinical stages. Evaluation of proliferative status of RCC is a useful adjunct as a prognostic parameter as it is seen to correlate well with both clinical stage and nuclear grade. In our study, MVD was not seen to correlate with either of these.

Study of the telomerase hTERT fraction, PCNA and CD34 expression on pituitary adenomas. Association with clinical and demographic characteristics

To determine the frequency of human telomerase reverse transcriptase (hTERT) catalytic fraction expression and its association with clinical and demographic characteristics of the patient, as well as with the expression of CD34 and proliferating cell nuclear antigen (PCNA) indexes on adenohypophyseal hormone tissues. A transverse study was realized with 49 cases of hypophyseal adenoma with analysis type cases and controls. The different adenohypophyseal hormones [prolactin (PRL), growth hormone (GH), follicle stimulating hormone, luteinizing hormone, thyroid gland stimulant hormone, adrenocorticotropic hormone (ACTH)], the catalytic fraction of the telomerase hTERT, the PCNA index and the CD34 density were determined by means of immunohistochemical techniques. The clinical, demographic and histopathological characteristics of the patients with and without hTERT expression were compared by means of Pearson's Chi-squared, Fisher's exact test and Mann-Whitney's U. Twenty-eight point six percent of the adenomas had positive expression for hTERT. The variables significantly correlated with hTERT's expression were younger age of presentation, diagnostic of adenoma producer, higher PCNA index, higher CD34 density, increased GH on serum and the expression on PRL tissue, GH and ACTH. Tobacco history had a negative association with hTERT's expression. The telomerase could be a marker of cellular proliferation associated with angiogenesis and hormonal activity. Evaluation of these variables could provide information about their biological behavior.

Fas Ligand Expression and Its Correlation with Apoptosis and Proliferation in Lobund-Wistar Prostate Carcinomas

Objective: The Fas (CD95) interaction with its receptor Fas ligand (FasL) is one of the main mechanisms of cell apoptosis. High expression of FasL has been consistently observed in a variety of human cancers. In this study, we evaluated FasL and its relationship with apoptosis and proliferation in Lobund-Wistar (L-W) cancers. The L-W rat strain develops spontaneous and induced adenocarcinomas in the anterior prostate and seminal vesicles. Although FasL expression has been observed in a subset of human prostate carcinomas, this multistage model allowed in vivo evaluation of subclones of malignant cells with a single genetic susceptibility. Methods: Apoptosis was evaluated in spontaneous, induced and transplanted tumors as well as metastasis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique and transmission electron microscopy. Proliferating cell nuclear antigen (PCNA) and FasL expression were detected using immunohistochemistry and analyzed according to the number of positive cells and intensity of staining using a semiquantitive method. Results: Apoptotic indexes were significantly higher in spontaneous tumors compared to induced (p < 0.008), transplanted tumors (p < 0.0112) and metastases (p < 0.009). TUNEL-positive cells were frequently observed in the leukocytic infiltrate of the stroma in transplanted carcinomas and metastases. These findings were confirmed by electron microscopy. FasL expression was not uniformly localized in L-W carcinomas and its highest expression was observed in transplanted tumors and metastasis (p < 0.005). Moreover, PCNA indices were directly correlated with cancers showing high FasL total scores (Hscores). Conclusions: In this model, high FasL expression was associated with cells displaying low apoptotic indexes and high PCNA index. Therefore, analysis of FasL may have clinical relevance in detecting the malignant potential of prostate cancers.

Preoperatively Irradiated Rectal Carcinoma: Analysis of the Histopathologic Response and Predictive Value of Proliferating Cell Nuclear Antigen Immunostaining

Objectives: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53. Methods: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy. Results: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07–26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy. Conclusion: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy.

Characterization of myocardial hypertrophy by DNA content, PCNA expression and apoptotic index

Background: At present little is known about the biological basis of cellular alterations in myocardial hypertrophy. The present study aims to analyze proliferating cell nuclear antigen (PCNA) expression, DNA content and apoptosis, in several types of myocardial hypertrophy in order to define the biological characteristics of this process. Methods: The biological parameters were investigated in normal hearts ( n=4) and in 21 cases of left ventricular myocardial hypertrophy related to pressure overload ( n=7), post-infarction remodeling ( n=8) and hypertrophic cardiomyopathy (HCM) ( n=8). Results: The analyzed biomarkers were similar in hypertension and in remodeling, with a very high apoptotic index (mean values: 8.1 and 8.5%, respectively), a low PCNA positivity (mean values: 1.8 and 1.6%) and a prevalent diploid DNA content (DNA index: 1.2). Conversely, HCM showed a high mean PCNA index (21.2%) associated with a prevalence of hyperdiploid myocytes (DNA index: 1.8) and a low number of apoptotic cells (mean value: 1.7%). Conclusions: There are significant biological differences between hypertrophy in HCM and that related to arterial hypertension and post-infarction remodeling. Therefore, the combined evaluation of DNA content, PCNA and apoptotic indices could provide a powerful diagnostic tool in doubtful cases of myocardial primary or secondary hypertrophy and open new avenues in the clinical treatment of these entities.

Prognostic value of proliferating cell nuclear antigen immunostaining in pediatric rhabdomyosarcomas.

The levels of proliferating cell nuclear antigen (PCNA) are almost negligible in long-term quiescent cells and increase dramatically during the cell cycle. Recently, the monoclonal antibodies to PCNA have been used to demonstrate the proliferative component of paraffin-embedded tumor tissues. It has been shown to be available as a simple histological marker of proliferative activity and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin fixed, paraffin embedded tissue specimens of 29 primary pediatric rhabdomyosarcomas were immunostained by using an anti-PCNA monoclonal antibody (DAKO PCNA PC10). The relationship between the PCNA index and prognosis, clinicopathological features and survival were assessed retrospectively. The mean PCNA index for the whole series was 54%. There was no correlation between PCNA index and any of the clinicopathological characteristics. However, patients having tumors with a high (> 54%) PCNA index demonstrated significantly lower survival rates than tumors with a low (< 54%) PCNA index (P = 0.01). Moreover, there were significantly more patients with relapse or progressive disease in the high PCNA index group (P = 0.005). The PCNA labeling index can be a useful prognostic factor and a good indicator of recurrence and/or survival in patients with rhabdomyosarcoma.

Adrenocorticotropin-Producing Pituitary Carcinoma with Expression of c-erbB-2 and High PCNA Index: A Comparative Study with Pituitary Adenomas and Normal Pituitary Tissues.

Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing's disease resulting from a pituitary carcinoma in a 22-yr old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing's disease (n = 52), other pituitary adenomas (n = 292). and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis. C-erbB-2 staining was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular immunohistological type preferentially expressed this protein. In normal pituitary tissues, 10% of the cells expressed cytoplasmic c-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4 -t 1 S% vs 1 ii +/- 1.5% in noninvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). The PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p(2ras) was negative in the carcinoma and liver metastasis. We suggest that the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.

Significance of trisomy 7 related to PCNA index in cholesteatoma

Purpose: To define the biological features of the variable aggressiveness of cholesteatoma, we performed a retrospective cytogenetic and kinetic study. Materials and Methods: We studied 44 cases of cholesteatoma by using fluorescence in situ hybridization with specific a-satellite DNA probes for chromosome 7 and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) with PC10 monoclonal antibody. Results: We observed the presence of three or four chromosome 7 in elevated percentages of cells of 23 cases, and a high PCNA index (above mean value) in 22 cases. Conclusion: Based on our results, we maintain that the presence of an extra chromosome 7 is correlated with an increase of proliferative activity. Therefore, trisomy 7 can be considered a prognostic marker and an indicator of aggressive behavior in cholesteatoma.

Correlated Expression of BCL-2 Protein, Estrogen Receptor, Cathepsin D and Low Growth Fraction (PCNA) in Intracystic Papillary Breast Carcinoma

The expression of BCL-2 protein was evaluated immunohistochemically in 23 intracystic papillary carcinomas (IPCs) of the breast. Twenty-two patients were female and one male, aged 49-90 years (median 72). Twenty-one cases had a benign behaviour, while two cases developed local recurrence. Of the 23 tumours, 19 (82%) were immunoreactive for BCL-2, the majority of positive carcinomas showing intense cytoplasmic staining of more than 50% neoplastic cells. The intensity of BCL-2 expression was significantly correlated with prognostic markers such as estrogen receptor (ER) positivity (p = 0.001), cathepsin D (CD) reactivity in the neoplastic cells (p = 0.001) and low growth fraction, evaluated by proliferating cell nuclear antigen (PCNA) immunostaining (p = 0.008). An inverse relationship was also found between BCL-2 and p53 protein (p = 0.001). Three cases of high grade (G3) IPC expressed p53, high PCNA index, and CD (the latter only in the stromal cells), but no immunostaining for BCL-2 and ER. Thus, absence of BCL-2 expression in high grade IPC was associated with ER-negative, rapidly proliferating and p53-positive immunophenotype. All high grade tumours showed invasion of the cystic wall. Local recurrence developed in one of these. The authors conclude that BCL-2 immunoreactivity in IPC is related with tumour grade and with a range of molecular markers of favourable prognosis such as ER positive status, CD expression in the neoplastic cells, and low PCNA index. These findings are consistent with the indolent clinical course and the very favourable prognosis of IPC of the breast.

Proliferating Cell Nuclear Antigen in Endometrial Carcinoma: Pretreatment Identification of High-Risk Patients

Objective: The aim of our study was to retrospectively examine the proliferating cell nuclear antigen (PCNA) immunoreactivity of tumor cells in curettage specimens containing endometrioid adenocarcinoma and obtained immediately before definitive surgical staging. This PCNA index was compared with the one subsequently derived from surgical specimens and assessed as a function of histologic grade, depth of myometrial invasion, neoplastic nodal involvement, cervical spread, and progression-free survival in order to determine a new prognostic parameter valuable at the time of diagnosis. Materials and methods: A population of 79 patients with locally advanced (stage I and II) endometrioid carcinoma, who underwent both the preliminary diagnostic curettage and the subsequent definitive surgical management, selected from January 1986 to June 1993 at the Department of Gynecology and Obstetrics, Ancona University, was retrospectively recruited from our series of 99 endometrial carcinomas. The archival paraffin blocks from the curettage and uterine specimens were identified and assessed for histologic reexamination and PCNA immunostaining [PC10 monoclonal antibody (Dako, Denmark)]. Results: After a median follow-up of 47 months, recurrences were detected in 7 cases, and the Kaplan–Meier disease-free survival curve estimated for the entire study group was 91%. The median PCNA index of the curettage specimens presented a good overlap with the PCNA immunostaining in corresponding uterine samples with a correlation coefficient of 0.4 (P= 0.02). A PCNA index ≥30% in curettage specimen was predictive of deep myometrial invasion; of 35 patients with PCNA index ≥30%, 29 (83%) had myometrial invasion ≥50%. No significant relationship was observed with neoplastic cervical spread, and histologic differentiation. By Cox hazard analysis, the PCNA index evaluated on curettage specimens was significantly related to disease-free survival, with significant disease-free survival advantages for patients with PCNA <30% (P<0.001). Conclusion: Our findings suggest that the PCNA immunostaining has proved to be considerably promising for the risk assessment in locally advanced endometrial carcinoma. The PCNA index is an objective and reproducible parameter accruably valuable also before starting the treatment; in presence of a high PCNA index, the patients should be referred to gynecologic oncologists for appropriate management.

Vimentin and proliferating cell nuclear antigen (PCNA) expression in node-negative breast carcinomas and their correlations with pathologic variables and prognosis

Abstract Vimentin and proliferating cell nuclear antigen (PCNA) immunohistochemical staining was performed in a series of 92 node-negative breast carcinomas and expression compared with tumour size, histological grade, nuclear grade, necrosis, lymphocytic infiltrate, oestrogen and progesterone receptors, and relapse rate. Vimentin was expressed in 13% of tumours and all positive cases were invasive ductal carcinomas. A strong relationship was noted between vimentin positivity, and both histological ( P = 0.01) and nuclear grade ( P = 0.02). The percentage of PCNA positive cells (PCNA index) varied from 0.2 to 70% (mean 27.45, median 28). PCNA index showed a significant correlation with histological ( P = 0.001) and nuclear grade ( P = 0.004). Furthermore vimentin positivity was significantly associated with high PCNA index ( P = 0.002). With univariate analysis vimentin positivity and high PCNA index (> 28) were both significantly correlated with shorter disease free survival ( P = 0.003 and P = 0.002 respectively) (median follow-up 84 months), while no other parameter reached significance. Using multivariate analysis PCNA index was statistically related to disease-free survival ( P = 0.05), whereas vimentin lost its significance. Our results suggest that PCNA may be useful in identifying node-negative breast cancer patients at risk of recurrence.

Prognostic Value of Proliferating Cell Nuclear Antigen (PCNA) Immunostaining in Neuroblastoma

Immunostaining for proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, is being increasingly used to study the proliferative activity of tumors, and the PCNA labeling index has been correlated with the prognosis of several malignant neoplasms. Formalin-fixed, paraffin-embedded tissue specimens of 24 primary neuroblastomas were immunostained using an anti-PCNA monoclonal antibody and the PCNA index was calculated. Then the relationship between the PCNA index, prognosis, and various other factors was assessed, retrospectively. The mean PCNA index was 11.0%. Patients having tumors with a high PCNA index (> or = 11.0%) showed a significantly lower survival rate than those possessing tumors with a low PCNA index (P < 0.001). Moreover, the tumors showing N-myc amplification had a high mean PCNA index of 15.6%, while those without N-myc amplification had a low mean index of 1.7% (P < 0.01). The PCNA index was closely related to the prognosis of neuroblastoma and to N-myc amplification. It has the potential to be a useful prognostic indicator of the patients with neuroblastoma.

PCNA immunostaining combined with AgNOR staining in esophageal squamous cell carcinoma to identify patients with a poor prognosis

Immunostaining of the proliferating cell nuclear antigen (PCNA) provides important information about cell kinetics and is easily performed on routinely obtained formalin-fixed, paraffin-embedded materials. We report herein the results of a retrospective study on PCNA staining in esophageal cancer undertaken to determine its significance. As this study indicated that immunoreactivity was preserved in specimens fixed within 24h, only 31 specimens from surgical patients were available for this investigation. The mean PCNA index of the patients without invasion to the adventitia (35.7 +/- 17.9) was significantly lower than that of those with invasion to the adventitia or neighboring structures (49.7 +/- 14.5), while the PCNA index did not correlate with other clinicopathologic parameters such as histologic type, lymph node metastases, or prognosis. However, when an analysis of PCNA staining was combined with an analysis of argyrophilic nucleolar organizer region (AgNOR) staining, a correlation with prognosis was found. In fact, seven patients with a high PCNA index (> or = 44) and AgNOR count (> or = 6) had a significantly poorer prognosis than the remaining 22 (P = 0.0014), and six of these seven patients died within 2 years. These results indicate that this combined evaluation may be useful for the identification of patients with a poor prognosis among those undergoing surgery for esophageal squamous cell carcinoma.

Expression of p53 protein, PCNA, and Ki-67 in osteosarcomas of bone.

Expressions of p53 protein, a product of the tumor suppressor gene were studied in osteosarcomas relating to various prognostic factors. Thirty-four osteosarcomas were investigated immunohistochemically with a monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins and another clone PAb1801, which reacts with both wild- and mutant-type p53 proteins. The results were compared with expressions of proliferating cell nuclear antigen (PCNA) and Ki-67 providing a simple method for the assessment of growth fractions of tumors. PAb240 stained nuclei and cytoplasm of tumor cells in 8 of 34 osteosarcomas (23.5%), whereas PAb1801 reacted in all 34 osteosarcomas (100%). Fifteen tumors (44.1%) showed positivity for PAb1801 in more than half of the tumor cells. Twelve patients were alive and thirteen were dead. Tumors from 9 patients (75%) who survived revealed only focal positive immunoreactions with PAb1801 and tumors from 6 patients (46.1%) who died revealed diffuse reactions. Twelve cases (35.3%) showed a high PCNA index (> 40%) and fibroblastic osteosarcomas revealed the highest PCNA positivity. Twenty-two cases (64.7%) revealed a very low Ki-67 index (less than 10%) and Ki-67 index showed a good correlation with PCNA positivity (r = 0.6247). Expressions of both wild-and mutant-type p53 protein, PCNA, and Ki-67 were not correlated with other clinical or pathological parameters.

Prognostic Value of Proliferating Cell Nuclear Antigen in Phyllodes Tumor of the Breast

The proliferating cell nuclear antigen (PCNA), a nuclear protein essential for cellular DNA synthesis, has been used to assess cellular proliferation in many tumors. To evaluate the potential value of PCNA in predicting the outcome of phyllodes tumor of the breast, we retrospectively studied 17 tumors diagnosed during the period 1985-1991. PC 10, a monoclonal antibody that recognizes PCNA, was applied to for malin-fixed, paraffin-embedded sections. The PCNA index ranged from 0.2% to 66.3%. The tumors were stratified into high (&gt;9.8%, n = 4) or low (≤9.8%, n = 13) PCNA index groups. No significant correlation between high PCNA index and the clinicopath ologic parameters with the exception of infiltrative margin was sound. However, the difference in recurrence-free survival between the two groups was significant (log rank test P &lt; .01). The Cox's regression analysis showed that high PCNA index was an important prognostic factor for tumor recurrence. PCNA staining could be used as an objective prognostic factor for the local recurrence of phyllodes tumor of the breast. Int J Surg Pathol 2(2):125-132, 1994

Proliferating cell nuclear antigen in needle biopsy specimens of prostatic carcinoma.

The expression of proliferating cell nuclear antigen (PCNA) was immunohistochemically determined using a monoclonal antibody PC10 in 54 prostatic carcinoma samples. The samples were taken from needle biopsy specimens which had been paraffin-embedded after routine fixation with 10% formaldehyde solution (formalin) for less than 24 h. The PCNA index was calculated as the percentage of positive tumor cell nuclei. There was a significant difference in the PCNA index according to the growth pattern (p < 0.001), nuclear anaplasia (p < 0.001) and T stage (p < 0.01). Regarding the growth pattern, solid carcinomas showed a significantly higher PCNA index than did either separate gland carcinomas (p < 0.05) or trabecular/fused gland carcinomas (p < 0.05). The PCNA index correlated closely with either the nuclear anaplasia or T stage, and increased in conjunction with the increased nuclear anaplasia (rs = 0.641; p < 0.001) or T stage (rs = 0.435; p < 0.01). The patients in the high PCNA index (> or = 15%) group showed a significantly worse survival than did those in the lower PCNA index group (p < 0.01), and multivariate analyses indicated that the PCNA index had an independent prognostic significance. These results suggest that the PCNA index, as determined by PC 10 on needle biopsy specimens of prostatic carcinoma, can thus be an objective and quantitative means for evaluating the biological malignancy of prostatic carcinoma.

PREDICTION OF THE PROGNOSIS OF PATIENTS WITH GASTRIC-CANCER BY ERBB-2 TISSUE STATUS AND EXPRESSION OF PROLIFERATING CELL NUCLEAR ANTIGEN

Correlation between erbB-2 tissue status and expression of proliferating cell nuclear antigen (PCNA) was studied in 164 gastric carcinomas, and these results were compared with the risk of metastasis and prognosis. Thirty-one (19%) tumors showe evidence of erbB-2 protein expression, and the PCNA index ranged from 8.2% to 77.2% (mean; 40%). erbB-2 protein positive tumors were most often encountered in the following clinicopathological groups: tumors with serosal invasion, lymph node metastasis, and venous invasion. There was a significant correlation between PCNA index and lymph node metastasis. In addition, erbB-2 positive tumors showed significantly higher PCNA index than erbB-2 negative tumors. Cox prortional hazard model identified lymph node metastasis. In invasion, liver metastasis, and erbB-2 tissue status as independent prognostic factors, but PCNA index was not an independent prognostic factor. However, by combining erbB-2 tissue status and PCNA index, PCNA index. was a good prognostic factor particularly in patients with erbB-2 negative tumors. These results indicate that the determination of erbB-2 tissue status, when combined with PCNA index, may be useful in the prediction of the prognosis and in deciding the therapeutic schedule of patients with gastric cancer.

Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence

The recurrence rate of pituitary adenomas has been reported to be as high as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) was used to investigate whether the proliferative index might help to predict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, and its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrecurrent adenomas, and seven normal pituitary tissue samples. The mean interval to recurrence ( +/- standard error of the mean) was 5.3 +/- 0.7 years. The age- and sex-matched nonrecurrent group had a mean follow-up period of 6.6 +/- 0.3 years without clinical recurrence. Mean percentages of PCNA-positive tumor nuclei in both the initial and the second surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 19.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumors had a higher PCNA index than the initial tumors in the same patients. Normal anterior pituitary gland tissue had a significantly lower mean PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise multivariate regression analysis indicated that factors which collectively correlated significantly with recurrence were: high PCNA index, large tumor size, extrasellar extension, and incomplete surgical excision. The PCNA nuclear count was not associated with age, sex, or hormone hypersecretion, but was higher in macro- than in microadenomas, in tumors with extrasellar extension, and in those incompletely excised. A higher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in predicting the likelihood of pituitary adenoma recurrence.