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Biomedical subjects

I A Sesterhenn

Publications and source records attributed to I A Sesterhenn.

At least 55 records · Page 3Linked to original sources
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

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.

Aged↗
PubMed1998

Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl-2 oncogene in primary testicular germ cell tumours.

The role of p53 in testicular germ cell tumours is still contradictory based on the finding of immunohistochemical overexpression at the protein level, but lack of mutations at the DNA level. In addition, p53 wild-type activity has been demonstrated in cell culture experiments. Overexpression of the proto-oncogene bcl-2 might block p53-induced apoptosis and might inhibit p53 functional activity. To clarify the apparent paradox with respect to p53 overexpression and lack of mutations, an immunohistochemical and mutational analysis of p53 and bcl-2 in TGCT was performed. Ten normal testes, 52 CIS and 151 clinical stage I nonseminomatous GCTs were included in our study. A commercially available anti-p53 polyclonal rabbit antibody and an anti-bcl-2-mouse monoclonal antibody were used to stain the 5pm sections. Staining was assessed by counting at least 500 cells from the area of the most intense staining in each tumour cell type, and this was scored semiquantitatively for intensity of staining on a 4 point scale. In addition, 30 primary GCTs were included in the mutational analysis: areas with p53 overexpression were identified and microdissected prior to DNA extraction. p53 exons 5-8 were amplified by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis. Templates demonstrating band shifts on SSCP were subjected to direct DNA sequence analysis. None of the normal testes, 32/52 (62%) CIS, and 142/151 (94%) germ cell tumours exhibited p53 overexpression. p53 expression was significantly lower in mature teratomas (0.8 +/- 0.2) than in other germ cell tumour components (2.8 +/- 1.2, p > 0.001). PCR-SSCP did not reveal any missense mutations or deletions for the p53 gene. Bcl-2 protein expression was observed in none of the normal testes, in none of the CIS, and in 14/151 (9.3%) germ cell tumours. 13/14 germ cell tumours demonstrated bcl-2 expression only in the glandular and stromal elements of their teratomatous components whereas all other components were negative for bcl-2. Our results--p53 overexpression, lack of p53 mutations, undetectable bcl-2--are consistent with recent in vitro studies. High susceptibility of testicular cancer to drug-induced apoptosis appears to be the result of wild-type p53 and lack of bcl-2. Radiation and chemotherapeutic insensitivity of mature teratomas might be the result of bcl-2 overexpression and lack of p53 overexpression. Therefore, chemoresistance to DNA damaging agents might be reflected by the expression of p53 and bcl-2 and it might be useful to evaluate p53 and bcl-2 in primary tumours and metastatic lesions in order to identify patients early with primary or secondary chemoresistance.

Animals↗
PubMed1998

CD34 immunohistochemical assessment of angiogenesis as a prognostic marker for prostate cancer recurrence after radical prostatectomy.

PURPOSE: We assess the neovascularity of clinically localized prostate cancer by immunohistochemistry using the monoclonal antibody CD34 in an attempt to identify associations between angiogenesis and disease progression following radical prostatectomy. MATERIALS AND METHODS: Microvascularity was evaluated using the CD34 monoclonal antibody in archival paraffin embedded radical prostatectomy specimens from 149 patients followed from 3 to 10 years (mean 6.6). Vessels were quantified by counting a minimum of 2 selected microscopic fields (200x, 0.754 mm.2) from each tumor, area of prostatic intraepithelial neoplasia and prostatic hyperplasia, and given a numerical value representing the microvessel density count. RESULTS: Mean microvessel density count did not vary significantly with age or race. There was a significant association between the count and nuclear grade, Gleason sum and pathological stage. Cox survival analysis shows that microvessel density is significantly related to time to recurrence when considered as a continuous variable (p=0.03) as well as dichotomous variable (p=0.007) (microvessel density count less than 90 and 90 or greater). The 5-year recurrence-free survival was significantly higher for patients with a count less than 90 (71%) than for those with a count 90 or greater (51%) (p=0.006). The 5-year recurrence-free survival was also significantly different when microvessel density was used as a continuous variable (p=0.02). Controlling for stage, Gleason sum, race and nuclear grade, microvessel density remained significant in predicting recurrence (p=0.03) but when pretreatment prostate specific antigen was included in the model the count was no longer significant. The microvessel density count in the tumor area significantly increased with increasing Gleason sum and nuclear grade but it did not increase significantly in the adjacent benign prostate or areas of prostatic intraepithelial neoplasia in the same specimen. CONCLUSIONS: Microvascularity or neovascularity as measured by the CD34 antigen may be a prognostic marker of recurrence for prostate cancer patients after radical prostatectomy but more study in prostate specific antigen era patients with sufficient followup is needed.

Age Factors↗
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

Inhibition of the growth of pre-established subcutaneous tumor nodules of human prostate cancer cells by single injection of the recombinant adenovirus p53 expression vector.

We have previously described potent growth-inhibitory effect of a recombinant adenovirus expressing wild type p53 (AdWTp53) in metastatic prostate cancer cells via activation of cellular p53 pathways. We have extended these observations to analyze the effects of AdWTp53 on primary cultures of radical prostatectomy specimens (RPS) and have also evaluated the gene therapeutic potential of the AdWTp53 in a nude mice model. Infection of primary cultures of prostate cancer specimens resulted in about 80% cell growth inhibition in comparison with cultures treated with control adenovirus dl312. Single injection of AdWTp53 into pre-established tumor nodules of DU145 prostate cancer cells suppressed tumor growth significantly (p = 0.0407) as determined by comparison of tumor volumes of the AdWTp53-treated vs. control vector (dl312) or PBS-treated groups. Moreover, there was no significant difference in tumor growth inhibition between single vs. multiple injections of AdWTp53. Our observations support the potential of AdWTp53 for gene therapy of prostate cancer.

Adenoviridae↗
PubMed1997

Biostatistical modeling using traditional variables and genetic biomarkers for predicting the risk of prostate carcinoma recurrence after radical prostatectomy.

BACKGROUND: Approximately 50-60% of patients treated with radical prostatectomy for clinically localized prostate carcinoma are found to have microscopic disease that is not organ-confined, and a significant portion of these patients will relapse. Multiple studies have attempted to identify these high risk patients by evaluating many potential prognostic variables. These studies, however, have not included the more recent molecular biomarkers found to be independent predictors of disease recurrence. METHODS: One hundred thirty-two patients who underwent radical prostatectomy at one center between 1986 and 1993 were subjected to a multivariable Cox regression analysis to determine the preoperative and postoperative variables that remain significant predictors for the likelihood of serologic recurrence. The preoperative variables included in the model were age, race, and prostate specific antigen(PSA); the postoperative variables were Gleason sum, nuclear grade, pathologic stage (capsular status), p53 tumor suppressor gene expression, bcl-2 protooncogene expression, and proliferative biomarker Ki-67 expression. Biomarkers were also evaluated separately. RESULTS: A model was developed using only variables that remained significant predictors for the likelihood of recurrence. The following equation calculated the relative risk of recurrence: Rw = exp [(0.70 x Race) + (0.79 x PSA[4.1-10]) + (1.34 x PSA[>10]) + ( 0.91 x Organ confinement) + (0.65 x p53[1,2+]) + (1.45 x p53[3,4+]) + (0.70 x bcl-2)]. This equation categorized men into 3 distinct risk groups (low: Rr < 5.0; intermediate: Rr = 5.0-15.0; high risk: Rr > 15.0). CONCLUSIONS: This equation allows patients at high risk for PSA recurrence to be identified shortly after radical surgery. These patients at high risk for serologic recurrence and eventual progression may be considered for currently accepted adjuvant therapy or enrollment in clinical trials for the newer investigational therapies for locally advanced prostate carcinoma.

Aged↗
PubMed1997

Mutations of the p16 gene product are rare in prostate cancer.

BACKGROUND: The p16 gene product is a negative regulator of cell cycle and has been shown to be deleted or mutated in a number of tumor cell lines and primary tumors. The role of p16 in prostate cancer is not defined. Prostate cancer tissues and cell lines were evaluated for p16 gene alterations. METHODS: Five metastatic prostate cancer cell lines were analyzed for p16 gene structure and its expression by Southern and Northern blot analyses. Forty-one DNA specimens from 18 microdissected primary tumor specimens, adjacent normal tissues, and cell lines were amplified by polymerase chain reaction for p16 protein coding and splice junction sequences. Mutations were analyzed by single strand conformation polymorphism and DNA sequencing. RESULTS: DU 145 cell line exhibited a missense mutation in codon 84 (GAC to TAC). With the exception of previously reported polymorphism, no mutation was detected in p16 coding or splice junction sequences in primary prostate cancer specimens. CONCLUSIONS: Inactivation of p16 gene by mutations in the protein coding sequence does not play a major role in the genesis of primary prostate cancer.

Blotting, Northern↗
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

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

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↗
PubMed1996

Enumeration of interphase chromosomes. Comparison of visual in situ hybridization and confocal fluorescence in situ hybridization.

OBJECTIVE: To compare two visual enumeration methods to determine whether the confocal approach yielded better counts of chromosome-specific hybridization sites. STUDY DESIGN: Brightfield microscopy was used to count in situ hybridization (ISH) sites in 4-microns tissue sections. Confocal microscopy was used to collect three-dimensional (3D) data sets from fluorescence in situ hybridization (FISH) preparations made with sections of various thicknesses. Analysis of the confocal images relied on custom-built interactive visualization software. RESULTS: The confocal method yielded higher average counts of hybridization sites per nucleus due to fewer truncated nuclei in thicker sections and to visual exclusion of the truncated nuclei that remained. Optimal section thickness was 8-12 microns. Limited penetration by FISH reagents restricted the use of thicker sections. CONCLUSION: Analysis of intact nuclei visualized in three dimensions was more sensitive in demonstrating high centromere number than was brightfield ISH analysis of 4-microns sections. Improvements in semiautomated interactive software may make the confocal approach practical for accurate evaluation of chromosome number in precise histologic contexts.

Carcinoma, Transitional Cell↗