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F K Mostofi

Publications and source records attributed to F K Mostofi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Prognostic risk factors that identify patients with clinical stage I nonseminomatous germ cell tumors at low risk and high risk for metastasis.

BACKGROUND: The purpose of this study was to develop a reliable model to identify clinical Stage I nonseminomatous germ cell tumors (NSGCTs) associated with low risk or high risk for occult retroperitoneal metastasis, so that the model could be used to customize the therapeutic approach for patients with these tumors. The model was to be based on pathohistologic parameters and immunohistochemical expression of proliferation markers, proteases, and adhesion molecules in the primary tumor. METHODS: One hundred forty-nine patients with clinical Stage I NSGCTs underwent retroperitoneal lymphadenectomy and were included in the study. Three to five paraffin embedded, formalin fixed tissue blocks were available from each patient and were analyzed for the following histopathologic features associated with pathologic Stage I or II disease: the presence or absence of vascular invasion (VI), the presence or absence of tunic invasion, and the percentage of each histologic type present in the primary tumor. Immunohistochemical expression of MIB-1, p53, bcl-2, cathepsin D, and E-cadherin was evaluated using a semiquantitative scoring system. Statistical analysis was performed with univariate and multivariate logistic regression models. RESULTS: The percentage of embryonal carcinoma (%EC, P < 0.001) and the presence of VI (P < 0.0001) and tunic invasion (P < 0.002) were the most significant independent risk factors associated with pathologic Stage II disease. A combination of %EC and VI allowed correct prediction of final pathologic stage for 88% of clinical Stage I patients. Cutoff values including both variables identified the correct pathologic stage for 131 of 149 patients (88%). Less than 45% EC and the absence of VI correctly identified pathologic Stage I disease in 91.5% of patients; more than 80% EC and the presence of VI correctly predicted pathologic Stage II in 88%. In univariate analysis, only p53 (P < 0.03) and E-cadherin (P < 0.001) expression were significantly different in the embryonal carcinoma component of pathologic Stage I and II NSGCT. To evaluate prospectively the clinical utility of the new derived cutoff points, the data were applied to 10 consecutive patients with clinical Stage I NSGCT who underwent retroperitoneal lymphadenectomy; pathologic Stage I and II were correctly predicted for 5 of 6 Stage I and 4 of 4 Stage II patients, respectively. CONCLUSIONS: %EC and the presence or absence of VI appear to be reliable prognosticators to identify patients at high risk and low risk for occult retroperitoneal disease. In cases of clinical Stage I NSGCT, p53, bcl-2, MIB-1, cathepsin D, and E-cadherin did not appear to be of prognostic significance. The authors recommend that all patients with clinical Stage I NSGCT have their primary orchiectomy specimens evaluated for %EC and the presence of VI to determine their risk for occult retroperitoneal metastasis.

Antigens, Nuclear↗
PubMed1998

Immunohistochemical expression of monoclonal antibody 43-9F in testicular germ cell tumours.

The aim of this study was to evaluate the clinical utility of immunohistochemical staining of human testicular germ cell tumours with the monoclonal antibody 43-9F to distinguish embryonal carcinoma (EC) from other malignant germ cell components in order to facilitate pathohistological assessment of prognostic risk factors for metastatic disease in clinical stage I NSGCT. Archival, formalin-fixed, paraffin-embedded tissue blocks of 24 classical seminomas, 7 spermatocytic seminomas, and 20 non-seminomatous germ cell tumours were stained for 43-9F, AFP, hCG and PLAP expression. Immunohistochemical expression was graded using a semi-quantitative scoring system: 1+ = 0-25%, 2+ = 26-50%, 3+ = 51-75% and 4+ = 76-100%. Positive immunohistochemical staining for 43-9F was found in all embryonal carcinomas and yolk sac tumours (YST); staining intensity was not statistically different between the two tumours (3.8 +/- 1.2 vs. 3.1 +/- 0.9). Classical seminomas and seminomatous components of NSGCT stained positive in 13/24 cases (54%); staining intensity was weak to moderate (1.1 +/- 0.7) in all but two cases (4+). Spermatocytic seminomas demonstrated weak positive immunostaining in 2/7 cases (29%). Adjacent CIS was found in 33/54 (61.1%) of tumours and 24/33 (72.7%) of CIS cells exhibited a weak to moderate staining intensity (1.4 +/- 0.7). AFP expression was found in 93% of YST and in only 10% of EC; however, based on the focal staining pattern, adequate differentiation of YST and EC was not possible. Positive PLAP staining was observed in 75% of EC, 79% of seminomas and in 88% of CIS cells. We did not find 43-9F staining clinically useful to distinguish embryonal carcinoma from other germ cell tumour components such as yolk sac tumour. The detection rate of CIS by 43-9F immunohistochemical staining was low and combination of PLAP staining with light microscopy was even superior. Additionally, our study confirms the link between pre-invasive CIS and embryonal carcinoma and suggests the possible direct development of embryonal carcinoma from CIS.

Alkaline Phosphatase↗
PubMed1998

Angiomyofibroblastomalike tumor of the male genital tract: analysis of 11 cases with comparison to female angiomyofibroblastoma and spindle cell lipoma.

The clinicopathologic features and immunoprofile of 11 cases of an uncharacterized male genital tract tumor with features of vulvovaginal angiomyofibroblastoma (AMF) and spindle cell lipoma (male AMF-like tumor) are described. The lesions presented as a mass involving the scrotum (six cases) or inguinal region (five cases) in males ranging in age from 39 to 88 years (median 57). The tumors were superficially located and well-marginated and ranged in size from 2.5 to 14 cm (approximate mean 7 cm). Microscopically, they were composed of tapered spindled cells proliferating between numerous small to medium-sized vessels. Epithelioid appearing stromal cells were a focal finding in four cases. Mitotic activity was minimal with no abnormal mitotic figures identified. Mild nuclear atypia was identified in two cases. The tumors possessed an acid mucopolysaccharide-rich, finely collagenous stroma. A small quantity of intralesional fat was present in six cases. Tumor cells exhibited immunoreactivity for vimentin (seven of seven cases), progesterone receptor protein (five of seven cases), CD34 (four of eight cases), estrogen receptor protein (three of seven cases), desmin (three of eight cases), muscle-specific actin (three of eight cases), and smooth-muscle actin (two of eight cases) but not for S-100 protein. One of seven patients with follow-up after simple excision had recurrent/persistent disease. The male AMF-like tumor is a soft-tissue neoplasm of the male genital tract that shares clinicopathologic features and a proposed perivascular stem cell derivation with both the female angiomyofibroblastoma and spindle cell lipoma.

Adult↗
PubMed1998

The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee.

This WHO/ISUP system is an attempt to develop as broad a consensus as possible in the classification of urothelial neoplasms, building upon earlier works and classification systems. It is meant to serve as a springboard for future studies that will help refine this classification, thus enabling us to provide better correlation of these lesions with their biologic behavior using uniform terminology.

Carcinoma, Transitional Cell↗
PubMed1998

The molecular characteristics of bladder cancer in young patients.

PURPOSE: The molecular characteristics of bladder cancer in children and young adults remain largely undefined. We sought to identify common molecular changes in bladder tumors in young patients using standard immunohistochemical and interphase cytogenetic methods. MATERIALS AND METHODS: We retrospectively evaluated 73 bladder tumors removed from patients younger than 30 years for the p53 tumor suppressor gene product using immunohistochemical techniques and numerical aberrations of chromosomes 9, 17, X and Y. RESULTS: Regardless of stage, immunohistochemical evidence of p53 gene product over expression was found in the majority of tumors studied. Numerical aberrations (monosomy) of chromosome 9 were rare. Aneuploidy of chromosome 17 was common, particularly in carcinoma in situ and invasive bladder cancer. CONCLUSIONS: These data suggest that immunohistochemical evidence of p53 gene product over expression is common in bladder cancer in young patients. Further prospective analysis of lesions in this population may help to establish a comprehensive molecular progression model for urothelial neoplasms.

Adolescent↗
PubMed1997

Observations on the early detection of prostate cancer from the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) was established in 1987. The experience of the ACS-NPCDP demonstrates the yield and impact of periodic examinations for the early detection of prostate cancer. METHODS: A cohort of 2999 well men ages 55-70 years was tested annually at 10 clinical centers by prostate specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). Biopsies were performed on men with suspicious findings. Pathologic findings were reviewed. The initial study outcomes were the detection yield of multimodality testing and the comparative sensitivity and specificity of the different tests employed. Longer term outcomes included patient quality of life and survival. RESULTS: The cancer detection rate declined significantly across the years of intervention. DRE had lower sensitivity than TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that of DRE. Fewer than 9% of the cancers detected in this study were clinically advanced at the time of diagnosis. Ninety-four percent of patients in whom cancer was detected are alive after an average follow-up of 54 months. In one case, death occurred after surgery. Two deaths were attributed to prostate cancer, and eleven other deaths were unrelated to prostate cancer or its treatment. CONCLUSIONS: Results of the ACS-NPCDP indicate that a combined-modality approach to prostate cancer detection yields high levels of early detection with infrequent adverse outcomes. Continued follow-up is required to evaluate long term morbidity and mortality.

Aged↗
PubMed1997

Comparison of serum prostate specific membrane antigen, prostate specific antigen, and free prostate specific antigen levels in radical prostatectomy patients.

BACKGROUND: Higher preoperative prostate specific antigen (PSA) levels are associated with higher pathologic stage and grade in patients undergoing radical prostatectomy (RP). In earlier studies, serum prostate specific membrane antigen (PSMA) elevations were associated with clinical progression and hormone-refractory carcinoma. The goal of this study was to evaluate the serum markers PSMA, free PSA (FPSA), free:total PSA ratio (F:TPSA), and total PSA (PSA) in men undergoing RP. METHODS: Serum was obtained from 63 patients undergoing RP for clinically localized (T1c, T2) prostate carcinoma. Serum PSA and FPSA were determined by Hybritech Tandem-E(R) and Tandem-R(R), respectively, and PSMA was determined by Western blot analysis. Serum values for these markers were compared with the pathologic stage, surgical margin status, Gleason sum, prostate size (as calculated via reconstruction and transrectal ultrasound), tumor size based on pathologic assessment of the whole mount, and World Health Organization (WHO) grade of the prostatectomy specimen. Markers were also compared against demographic information and the patients' age and race. RESULTS: There was a weak correlation between serum PSA and positive surgical margins, higher Gleason sum, and WHO grade (P < 0.05). Receiver operating characteristic curve (ROC) analysis comparing sensitivity and specificity of the markers to positive and negative margins as well as seminal vesicle invasion demonstrated PSA and FPSA predictive ability for seminal vesicle invasion. The area under the curve for PSA and FPSA in this case was 0.7318 and 0.7432, respectively. There was also a weak correlation between the FPSA level and margins, with a low ROC area under the curve of 0.6789. The FPSA cannot distinguish the more advanced stage of disease. There was no significant correlation between F:TPSA and PSMA with regard to the study variables in predicting organ confinement. High PSMA levels only correlated with higher stage and were maximal in pT4a classified disease. CONCLUSIONS: Higher PSA and FPSA levels are likely to be associated with more locally advanced disease. Total PSA was the best marker. However, the cutoff values necessary for significant accuracy between PSA and FPSA are not of clinical usefulness due to the lack of specificity and sensitivity of the markers at those cutoffs. F:TPSA and PSMA levels as currently measured are of limited value in discriminating more aggressive disease in patients with clinically localized CaP.

Aged↗
PubMed1997

Prostate-specific antigen-detected prostate cancer (stage T1c): an analysis of whole-mount prostatectomy specimens.

BACKGROUND: Clinical and pathological staging of prostate cancer has been, and remains, problematic. Since prostate-specific antigen (PSA)-detected tumors are often discerned during "screening," what are their significance? METHODS: We analyzed 67 consecutive patients with stage T1c prostate cancer undergoing radical prostatectomy at our institution from August 1, 1991-September 12, 1995, and who had whole-mount specimen processing. Diagnosis was determined in all cases by transrectal ultrasound-guided biopsy. RESULTS: The mean age of our patients was 63 years, and the mean PSA at time of diagnosis was 8.6 ng/ml (median, 7.2 ng/ml). There was organ-confined cancer in 31/67 (46%) patients; 17/67 (25%) had periprostatic fat infiltration, and of these 5(7%) had seminal vesicle involvement. Thirty-one of 67 (46%) had positive surgical margins. Twenty-two (33%) had a Gleason sum of > or = 7 in the final pathological specimen. Insignificant tumors (dominant tumor volume < 0.20 cc) were found in only 4 cases. Smaller tumors were more likely to be found when the PSA was < 10 ng/ml. Multifocal disease was found in 64/67 (96%) prostate specimens. CONCLUSIONS: This study adds impetus to the growing realization that nonpalpable prostate cancer, detected because of elevated PSA, is rarely insignificant. Our findings add further emphasis to the fact that patients diagnosed by PSA elevation have, for the most part, significant cancer that should be treated aggressively.

Aged↗
PubMed1997

[Clinical stage I mature teratoma of the testis--retroperitoneal lymphadenectomy or surveillance?].

Pure teratomas are considered to be less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratomas are considered to be candidates for surveillance protocols. We report on the clinical history and treatment of 44 patients with a primary pure testicular teratoma. In all, 35 patients (79.5%) presented with clinically low-stage disease [n = 26, clinical stage I (59.1%); n = 9, clinical stage IIA/B (20.4%)] and underwent radical orchiectomy followed by retroperitoneal lymphadenectomy (RPLND); nine patients (20.5%) presented with clinically advanced disease (clinical stage IIC to stage IV). Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. The frequency of lymph node metastases in patients with clinical stage I disease was 19.2%; in patients with clinical stage IIA/B the risk was 66%. Pathohistological diagnosis of mature teratoma was confirmed in all cases; however, 17/20 patients demonstrated scars or calcifications in the adjacent parenchyma, indicating a burned-out tumor and 3/20 demonstrated microfocal germ cell tumor elements. None of the clinical stage I patients relapsed during follow-up; relapse rate among patients with stage IIA/B disease was 33%. Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results, metastases in testicular mature teratoma seem to result from metastazising non-germ-cell components undergoing early regression as demonstrated by the high frequency of burnedout tumors. We recommend serial sections of the orchiectomy specimen in all cases of pure mature teratoma for deciding on adequate management: RPLND in cases with associated scars, calcifications or microfocal malignant germ cell components, and surveillance in cases with pure mature teratomas.

Aftercare↗
PubMed1997

Incidence and clinical significance of high-grade prostatic intraepithelial neoplasia in TURP specimens.

OBJECTIVES: To determine the incidence and clinical significance of high-grade prostatic intraepithelial neoplasia (PIN) in specimens obtained from transurethral resection of the prostate (TURP). METHODS: All TURP specimens accessioned to the general surgical pathology service of the Johns Hopkins Hospital (JHH) from March 1984 through December 1987 that did not contain adenocarcinoma of the prostate were reviewed for the presence of high-grade PIN (PIN 2 and PIN 3). These cases were supplemented with cases from the consultation files of the JHH, the Armed Forces Institute of Pathology, and the University of Michigan Hospitals. In total, 85 cases of high-grade PIN in TURP specimens were identified. RESULTS: The mean age of the patients at the time of TURP was 70 years and the median age was 71 years (range 50 to 89). Sixty-three patients (74%) were 65 years of age or older, 45 patients (53%) were at least 70 years of age, and 14 patients (16%) were 60 years of age or younger. Adenocarcinoma of the prostate was discovered in 9 (22%) of 41 patients with follow-up information. Based on material from JHH, the incidence of high-grade PIN was 2.3% in all TURP specimens and 3.2% in those without invasive carcinoma. CONCLUSIONS: High-grade PIN on TURP is relatively uncommon and is diagnosed in an elderly population. Patients with high-grade PIN on TURP appear to be at increased risk of developing prostatic carcinoma, although not to the same degree as patients with high-grade PIN on needle biopsy.

Aged↗
PubMed1997

The role of retroperitoneal lymphadenectomy in mature teratoma of the testis.

PURPOSE: Pure testicular teratoma is rare in adulthood with an incidence of 5%. Pure teratoma is considered less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratoma have been considered candidates for surveillance protocols. We report our experience with 44 cases of primary pure testicular teratoma. MATERIALS AND METHODS: We retrospectively identified 44 patients (5.7%) with primary pure teratoma of the testis of the 772 treated for testicular germ cell tumors at our institutions. Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. A total of 35 patients (79.5%) who presented with clinical low stage disease, including stage I in 26 (59.1%) and stage IIA/B in 9 (20.4%), underwent radical orchiectomy followed by retroperitoneal lymphadenectomy. Nine patients (20.5%) who presented with clinically advanced disease (stages IIC to IV) were treated with primary chemotherapy and secondary retroperitoneal lymphadenectomy of residual masses. RESULTS: The frequency of lymph node metastases was 19.2% in clinical stage I disease and 66% in stage IIA/B. Histopathological diagnosis of mature teratoma was confirmed in all cases. However, of 20 patients 16 (80%) had scars or calcifications in the adjacent parenchyma, indicating a burned out tumor, and 4 (20%) had microfocal embryonal carcinoma. None of the patients with clinical stage I disease had relapse during followup and the relapse rate in those with stage IIA/B disease was 33%. Median followup was 97 months (range 24 to 250). Overall 43% of patients with pure teratoma presented with metastatic disease. CONCLUSIONS: Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results metastases in testicular mature teratoma seem to result from metastasizing nongerm cell components undergoing early regression, as demonstrated by the high frequency of burned out tumors. We recommend that serial sections be taken of the orchiectomy specimen in all cases of pure mature teratoma to determine adequate management: retroperitoneal lymphadenectomy in cases of associated scars, calcifications or microfocal malignant germ cell components and surveillance in cases of pure mature teratoma.

Follow-Up Studies↗
PubMed1997

Immunohistochemical expression of Ki-67 to predict lymph node involvement in clinical stage I nonseminomatous germ cell tumors.

PURPOSE: Primary archival tumor tissues of 89 patients with clinical stage I nonseminomatous germ cell tumors were analyzed for MIB-1 expression and histological parameters such as percentage embryonal carcinoma and presence of vascular invasion to determine the value of these parameters to predict absence or presence of occult lymph node disease. MATERIALS AND METHODS: A monoclonal antibody (MIB-1) developed for application in paraffin-embedded tissues was used to measure immunohistochemical expression of Ki-67 for the overall tumor (total MIB-1) and for each malignant cell type present. In addition, the primary tumors were examined for the presence of vascular invasion and determination of quantitative histology. Univariate and multivariate logistic regression models were used for statistical analysis. RESULTS: Univariate analysis neither revealed total MIB-1 score nor MIB-1 score in the highest area of staining of the different cell types to significantly predict pathological stage I or stage II disease. However, the presence of vascular invasion (p < 0.0001) and the percentage of embryonal carcinoma (p < 0.0001) were significant risk factors for occult nodal disease. Multivariate logistic regression analysis revealed the combination of vascular invasion and the percentage of embryonal carcinoma to be the best model to predict pathological stage II correctly (86.5%). DISCUSSION: The determination of immunohistochemical MIB-1 expression did not correlate with pathological stage in clinical stage I nonseminomatous germ cell tumors (NSGCT). We were not able to define high risk or low risk groups for occult nodal disease based on MIB-1 staining results. However, percentage of embryonal carcinoma and presence of vascular invasion accurately predicted absence or presence of lymph node metastasis in clinical stage I NSGCT. Our study underlines that a prospective multicenter trial is urgently needed to accurately assess the role of MIB-1 staining in management of clinical stage I NSGCT.

Antibodies, Monoclonal↗
PubMed1996

The results of a five-year early prostate cancer detection intervention. Investigators of the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary evaluation of early prostate cancer detection interventions. This report summarizes the experience of the investigators to date and describes the overall and relative performance of the different detection modalities studied in this project. METHODS: Two thousand nine hundred ninety-nine men aged 55 to 70 years at entry who were not already under evaluation for prostate cancer were recruited to participate in up to 5 annual examinations by prostate specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS). In the course of 5 years of intervention, ACS-NPCDP investigators have completed 9937 examinations, recommended 1215 biopsies, and detected 203 cancers. RESULTS: Loss to cohort follow-up was greatest in the first year. Overall, TRUS led to twice the number of recommendations for biopsy compared with DRE (8.9% versus 4.4%). Elevated PSA was observed in 13.0% of 9535 measurements performed. The overall cancer detection rate declined significantly during the five years of intervention. Detection was significantly associated with age and symptom status at entry. DRE had lower sensitivity compared with TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that for DRE. PSA was elevated in 69.2% of examinations that led to cancer detection, compared with only 10.9% when cancer was not found. PSA level, PSA density, and PSA change were all related to the presence of cancer. Less than 6% of the cancers detected in this study were clinically advanced at the time of diagnosis. CONCLUSIONS: These data quantify the yield of early cancer detection that may be expected when PSA, DRE, and TRUS are used in populations comparable to the men participating in the ACS-NPCDP. Continued follow-up and further research is needed to assess whether men receiving early prostate cancer interventions benefit as a result.

Aged↗
PubMed1996

Protein expression of p53, bcl-2, and KI-67 (MIB-1) as prognostic biomarkers in patients with surgically treated, clinically localized prostate cancer.

BACKGROUND: Protein expression in the primary tumor of the tumor suppressor gene p53 and the proto-oncogene bcl-2 have been shown to be prognostic biomarkers of cancer recurrence after radical prostatectomy in patients with clinically localized prostate cancer. Cancer cell proliferation as measured by immunohistochemical markers such as the MIB-1 antibody for Ki-67 has recently been suggested to be of prognostic value in prostate cancer. The goal of this study was to determine the clinical use of p53, Ki-67 (MIB-1), and bcl-2 immunohistochemical protein expression in the primary tumor as combined predictors of disease progression after radical prostatectomy (RP). METHODS: Protein expressions of p53, Ki-67, and bcl-2 were evaluated in archival paraffin-embedded RP specimens from 162 patients monitored from 1 to 10 years (mean, 4.5 years) and correlated to stage, grade, race, and serologic (prostate-specific antigen) recurrence after operation. RESULTS: Expression was detected in 112 (69.1%), 44 (27.2%), and 62 (38.3%) of 162 patients for p53 (1+ or greater), bcl-2 (1+ or greater), and Ki-67 (2+ or greater), respectively. Biomarker expressions were not correlated to age and race; however, all increased with increasing stage and grade. The degree of expression by percentage of malignant cells staining correlated to recurrence for p53 and Ki-67 but not for bcl-2. All three markers were correlated to raw and Kaplan-Meier recurrence by means of univariate analysis with recurrence estimates at 6 years of 60.7% versus 24.2%, 84.2% versus 38.6%, and 72.4% versus 30.6% comparing positive versus negative expression of p53, bcl-2, and Ki-67, respectively. p53 and bcl-2 remained as independent prognostic markers by Cox multivariate regression analysis. Although Ki-67 did not remain an independent marker, it added prognostic use in certain subsets of patients. CONCLUSIONS: p53, bcl-2, and Ki-67 (MIB-1) appear to be important biomarkers to predict recurrence in patients with clinically localized prostate cancer after RP, and all three biomarkers deserve further study.

Aged↗
PubMed1996

Ki-67 expression is a prognostic marker of prostate cancer recurrence after radical prostatectomy.

PURPOSE: We assessed the cellular proliferation of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody MIB to Ki-67 antigen in an attempt to identify associations between proliferative indexes and disease progression following radical prostatectomy. MATERIALS AND METHODS: Ki-67 proliferative antigen was evaluated using MIB 1 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 180 patients followed for 1 to 9 years (mean 4.4). The percentage of tumor nuclei expressing Ki-67 antigen was measured and assigned and MIB 1 score (none or rare--negative, 1+--low score and 2 to 4+--high score) and analyzed for prostate specific antigen, stage, age, race, grade and serological recurrence postoperatively. RESULTS: There was a significant association between MIB 1 score and nuclear grade (p < 0.001), Gleason score (p < 0.001) and pathological stage (p = 0.01). Patients with a high MIB 1 score had earlier progression and a lower 5-year recurrence-free survival rate (44%) than those with negative MIB 1 scores (71%, p < 0.001). In multivariate Cox regression analysis with backward elimination, pathological stage (p < 0.01), pretreatment prostate specific antigen (p = 0.04) and MIB 1 score (p = 0.05) were statistically significant predictors of disease-free survival, and patients with a high MIB 1 score were 3.1 times as likely to have recurrence as those with a negative score. Controlling for stage, patients with organ confined disease and a high MIB 1 score had a lower 5-year disease-free survival rate (68%) than those with a low MIB 1 score (95%, p < 0.01). CONCLUSIONS: Proliferative activity as measured by the Ki-67 proliferative antigen, MIB 1, appears to be a prognostic marker of recurrent prostate cancer after radical prostatectomy.

Aged↗
PubMed1996

Elevated levels of apoptosis regulator proteins p53 and bcl-2 are independent prognostic biomarkers in surgically treated clinically localized prostate cancer.

PURPOSE: The tumor suppressor gene (TSG) p53 and the proto-oncogene bcl-2 have been shown to be involved in the regulation of cell growth and apoptosis and have been implicated in hormone refractory prostate cancer (PC) and poor prognosis. The goal of this study was to determine the clinical utility of the presence of p53 and bcl-2 immunohistochemical (IHC) protein in the primary tumor as predictors of disease progression following radical prostatectomy (RP). MATERIALS AND METHODS: The expression of p53 and bcl-2 was evaluated in archival paraffin-embedded RP specimens from 175 patients followed from 1 to 9 years (mean = 4.6 years) and correlated with stage, grade, race and serologic (PSA) recurrence following surgery. RESULTS: Overexpression of bcl-2 was noted in 47 of 175 (26.9%) patients; these patients had a significantly higher 5-year failure rate than those who did not overexpress bcl-2 (67.0% versus 30.7%). Expression of p53 was noted in 114 of 175 (65.1%) patients with a 5-year failure rate of 51.1% compared with a 5-year failure rate of only 22% in p53 negative patients. When expression rates for p53 and bcl-2 were combined, the 5-year failure rate was 75.3%. Conversely, when both p53 and bcl-2 IHC staining were negative, the 5-year failure rate was 20.4%. Univariate Kaplan-Meier analysis showed a statistically significant difference between p53 and bcl-2 positive and negative patients (p < 0.001). Multivariate Cox Regression Analysis with backward elimination controlling for age, race, stage and grade showed both p53 (p = .0185) and bcl-2 (p = .004) to be independent predictors of disease-free survival. CONCLUSION: p53 and bcl-2 appear to be important biomarkers that predict recurrence in clinically localized PC after RP.

Aged↗