How should atypical prostate needle biopsies be reported? Controversies regarding the term "ASAP".
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Aged↗
Biomedical subjects
J I Epstein
Publications and source records attributed to J I Epstein.
Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer.
There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.
Adenocarcinoma↗
Incidental non-Hodgkin's lymphoma in patients with localized prostate cancer.
OBJECTIVES: To determine the outcome of patients with clinically organ-confined prostate cancer undergoing radical retropubic prostatectomy for cure and incidentally discovered concurrent low-grade non-Hodgkin's lymphoma at time of surgery. METHODS: From September 1986 to September 1997, 4319 patients underwent radical retropubic prostatectomy at our institution. The records of 10 patients incidentally diagnosed to have low-grade non-Hodgkin's lymphoma at the time of radical prostatectomy were retrospectively reviewed. RESULTS: Of 4319 patients requiring radical prostatectomy, 10 (0.2%) were found to have low-grade non-Hodgkin's lymphoma. All 10 men had an uneventful postoperative course. Two patients subsequently developed progression of lymphoma, one of whom required treatment. One patient died of sepsis associated with his lymphoma and 1 patient died of an unrelated malignancy (lung cancer), both 7 years following surgery. Two patients developed biochemical prostate-specific antigen recurrence. The remainder of men were free of prostate cancer recurrence and experienced no progression of lymphoma at an average of 45 months (range 12 to 142). CONCLUSIONS: Patients with organ-confined prostate cancer, who are candidates for radical prostatectomy, experience long-term prostate cancer-free survival in the face of incidentally diagnosed low-grade lymphoma. Because the management of most incidentally discovered low-grade lymphomas is expectant, patients discovered at surgery to have this clinical entity should not be denied radical prostatectomy.
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Nuclear morphometry adds significant prognostic information to stage and grade for renal cell carcinoma.
OBJECTIVES: Identification of patients with a high probability of recurrence after nephrectomy for renal cell carcinoma (RCC) is required for adjuvant studies of new therapies. Nuclear morphometry predicts prognosis for prostate, bladder, and Wilms' tumors and in RCC according to previous small pilot studies. METHODS: To validate this finding, we studied an additional 101 patients who underwent nephrectomy for Stage pT1 to pT3 RCC at our institution from 1977 to 1993 for whom data regarding recurrence or disease-free survival of greater than 60 months were available. Patient records and pathology specimens were reviewed. Of the 101 patients, 66 (65%) did not experience recurrence with greater than 60 months of follow-up, and 35 (35%) had RCC recurrence with a median time to recurrence of 17 months. Nuclear shape descriptors were tested as predictors of disease recurrence after accounting for stage and grade in proportional hazards regression models. RESULTS: Range of ellipticity (hazards ratio 3.39, P = 0.014) was confirmed to be a significant predictor of recurrence. A prognostic model using stage, grade, and range of ellipticity identified three distinct groups: low, moderate, and high recurrence risk groups, with recurrence rates of 4%, 37%, and 63%, respectively, at 5 years of follow-up. Morphometry significantly (P = 0.018) improved prognostication on the basis of stage and grade alone in this multivariate model. CONCLUSIONS: Nuclear morphometry is valid and accurate in predicting relapse in early-stage RCC. The model can select patients with RCC for adjuvant therapies.
Carcinoma, Renal Cell↗
Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease.
OBJECTIVES: To evaluate the relation between age, prostate-specific antigen (PSA) level, and the probability of detecting curable prostate cancer. METHODS: A consecutive surgical series of radical prostatectomies was performed in 492 men with nonpalpable (Stage T1c) disease, who formed the study cohort (mean age 58 years). The cohort was systematically classified into three age groups ([1] 40 to 50 years [n = 69]; [2] 51 to 60 years [n = 227]; [3] 61 to 73 years [n = 196]) and five pretreatment PSA groups ([1] 2.5 to 4.0 ng/mL [n = 36]; [2] 4.1 to 6.0 ng/mL [n = 100]; [3] 6.1 to 8.0 ng/mL [n = 122]; [4] 8.1 to 10.0 ng/mL [n = 76]; [5] greater than 10.0 ng/mL [n = 135]). The percent probability of curable cancer was determined by logistic regression analysis. Curable cancer was defined as organ-confined tumor or a tumor with capsular penetration of low grade (Gleason score less than 7), with negative margins and no involvement of seminal vesicles or lymph nodes. RESULTS: A comparison within age groups and within PSA groups revealed that the probability of curable cancer was more closely associated with age than PSA level. Although the probability of curable cancer was closely related to PSA level across a wide range of PSA values (0.4 to 52 ng/mL), there was only minimal difference (2% to 4%) in the probability of curable cancer within the range of PSA values from 2.5 to 6.0 ng/mL for all ages. CONCLUSIONS: Age is a strong predictor of the probability of curable cancer. Thus, early detection efforts in younger men are more likely to lead to a decrease in prostate cancer mortality. These data suggest that the use of PSA thresholds below 4.0 ng/mL as an indicator of prostate cancer is unlikely to improve the probability of detecting curable cancer.
Adult↗
Follow-up of atypical prostate needle biopsies suspicious for cancer.
OBJECTIVES: To determine both how the diagnosis of an atypical biopsy influences a urologist's decision to repeat the biopsy and the outcome of rebiopsy. METHODS: Of 200 atypical biopsies that we confirmed from outside consultations to the Johns Hopkins Hospital from 1992 to 1993, we were able to retrieve follow-up information for 144 cases. Each atypical biopsy was evaluated for the reason for atypia (atrophic glands, rule out [r/o] adenosis, atypical not otherwise specified [NOS; insufficient cytologic and/or architectural atypia], r/o prostatic intraepithelial neoplasia [PIN], inflammation, crush artifact) and a favored diagnosis (cancerous, benign, and undetermined). RESULTS: Of the 144 atypical biopsies, 92 were rebiopsied (63.9%). The time from the initial atypical biopsy to rebiopsy ranged from 0.5 months to 3 years (63% less than 6 months; 39% less than 3 months). Rebiopsy revealed carcinoma in 48.9%, benign in 38%, atypical in 8.7%, and PIN in 4.4%. The median prostate-specific antigen (PSA) value was lower in men who did not undergo a repeat biopsy (6 versus 7.8) (rank sum analysis, P = 0.04). No correlation was found between PSA level and results of the rebiopsy. Of the atypical biopsies in which cancer was favored, 61% were cancerous on rebiopsy versus 33% where a benign process was favored. The three reasons for atypical biopsies that seemed to correlate with outcome of rebiopsy were atypical NOS (68% cancer on rebiopsy); inflammation (63% cancer on rebiopsy); and r/o adenosis (36% cancer on rebiopsy). CONCLUSIONS: Although 48.9% of the rebiopsied cases were cancerous, only 63% of men underwent rebiopsy, raising a concern that cancers are being missed in those cases not rebiopsied after an atypical diagnosis. Although there was a trend for serum PSA to correlate with outcome of rebiopsy, this correlation was not significant, and even men with serum PSA less than 4 ng/mL had a 33% risk of cancer on rebiopsy. Although histologic features of the atypical foci may be useful as factors in determining the urgency for rebiopsy, they also were not statistically significant in predicting outcome. Men with atypical diagnoses should undergo rebiopsy regardless of serum PSA levels and regardless of why the lesions were atypical.
Adult↗
E-cadherin expression as a marker of tumor aggressiveness in routinely processed radical prostatectomy specimens.
OBJECTIVES: Approximately 30% of clinically localized prostate adenocarcinomas treated by radical prostatectomy (RP) will recur within 10 years. To prevent recurrence, new adjuvant therapies are in development that seek to treat high-risk patients after surgery. To identify patients as candidates for these treatments, improved biomarkers for predicting prognosis are needed. Reduced expression of E-cadherin has been proposed as a new marker for predicting prognosis in prostate adenocarcinoma. Since few studies have examined the relation between risk factors for disease progression and E-cadherin expression using routinely processed RP specimens, we used RP specimens to correlate downregulation of E-cadherin and pathologic stage at RP. METHODS: Primary adenocarcinomas (n = 76) from formalin-fixed and paraffin-embedded RP specimens were evaluated by immunohistochemistry against E-cadherin (HECD-1) using heat-induced epitope retrieval and automated staining (BioTek Solutions). Normal appearing prostate epithelium was used as an internal control for each specimen. Staining was scored as an estimate of the percentage of tumor cells in each specimen that showed strong plasma membrane staining. RESULTS: Specimens were divided into three categories with respect to Gleason score: intermediate (score 5 to 6, n = 31), intermediate to high (score 7, n = 25), and high (score 8 to 9, n = 20). For pathologic stage, specimens were divided into three categories: low stage/organ confined (pT2, n = 30), intermediate stage/limited extraprostatic extension (pT3a, n = 25), and high stage/seminal vesicle-pelvic lymph node metastases (pT3b-any pTN1, n = 21). In univariate analysis, reduced levels of E-cadherin correlated with advanced Gleason score (P = 0.003) and advanced pathologic stage (P = 0.008). In multivariate analysis, E-cadherin, preoperative prostate-specific antigen, and Gleason score all contributed independently to the prediction of high-stage disease (P<0.0001). Ten pelvic lymph node metastases from this same patient cohort were stained for E-cadherin. All were positive and 9 of 10 were moderately to strongly positive. CONCLUSIONS: Since essentially all patients in the high-stage category have a very high likelihood of disease recurrence, we conclude that the study of E-cadherin in a prospective manner as a potential biomarker of disease progression in patients with clinically organ-confined prostate cancer who undergo RP is warranted. Additionally, our finding that most metastatic tumor cells in pelvic lymph nodes express E-cadherin supports the notion that the establishment of the distant colonization and growth of metastatic tumor cells may be facilitated by expression or re-expression of previously downregulated E-cadherin. This would strongly suggest that irreversible genetic inactivation through mutation or allelic loss at 16q2.3 is probably not the mechanism of E-cadherin downregulation in most abnormally expressing primary prostate carcinomas.
Adenocarcinoma↗
Does long-term finasteride therapy affect the histologic features of benign prostatic tissue and prostate cancer on needle biopsy? PLESS Study Group. Proscar Long-Term Efficacy and Safety Study.
OBJECTIVES: Finasteride, a common agent used to treat benign prostatic hyperplasia (BPH), inhibits 5-alpha-reductase. Testosterone is converted by 5-alpha-reductase to the more potent dihydrotestosterone, which is the primary androgen in the prostate. Leuprolide is a stronger antiandrogen that is used to downstage prostate cancer before radical prostatectomy. Leuprolide induces marked atrophy of prostate carcinoma cells, which sometimes makes pathologic diagnosis of cancer difficult, although evaluation at radical prostatectomy is easier than at biopsy. It is unknown whether finasteride produces similar changes, which would result in greater diagnostic difficulty because such changes would be seen on biopsy to rule out cancer in men with suspicious clinical findings treated for BPH. The current study investigated the histologic effects of finasteride therapy on human prostate cancer and benign prostatic tissue on needle biopsy. METHODS: In blinded manner, we reviewed 53 needle biopsy specimens showing prostate carcinoma (35 treated with finasteride, 18 with placebo). Also reviewed in blinded manner were 50 benign needle biopsy specimens (25 treated with finasteride, 25 with placebo). The Gleason score, number of cores involved, percentage cancer involvement in a core, percentage of atrophic changes in cancer cells, presence of mitoses, blue-tinged mucinous secretions, prominent nucleoli, and high-grade prostatic intraepithelial neoplasia were documented for each case in the cancer group. The percentage of atrophy, basal cell hyperplasia, transitional metaplasia, chronic inflammation, and stromal proliferation was documented for each case in the benign group. RESULTS: No significant histologic differences were present in either the benign or cancer group between cases treated with finasteride and placebo. CONCLUSIONS: We conclude that finasteride treatment for BPH does not cause difficulty in the diagnosis of cancer in prostate needle specimens. It is possible that there are severely atrophic areas resulting from finasteride treatment that are undersampled. However, the conclusion that cancer seen on needle biopsy in men treated with finasteride is unaltered and readily identified as cancer remains valid.
Aged↗
Excision of the neurovascular bundle at radical prostatectomy in cases with perineural invasion on needle biopsy.
OBJECTIVES: To assess, in a group of patients who had undergone radical prostatectomy and who were likely to have extraprostatic extension of their tumors based on the previous finding of perineural invasion on needle biopsy, how effective excision of the neurovascular bundle was in reducing the number of positive margins and increasing the potential cure rate. METHODS: Eighty radical prostatectomy cases from our institution that had perineural invasion on prostate needle biopsy were retrospectively studied to determine the presence and location of extraprostatic extension, positive margins, and seminal vesicle or lymph node involvement, whether the neurovascular bundle had been excised, and whether tumor was present in the bundle region. RESULTS: In 14 (17.5%) of 80 cases, excising the neurovascular bundle led to a situation in which there was tumor in the neurovascular bundle, all the surgical margins of resection were negative for tumor, and there was no seminal vesicle or lymph node involvement. The remaining cases were equally divided between (a) less aggressive tumors that were organ-confined or had only focal extraprostatic extension with no tumor in the neurovascular bundle and (b) more aggressive tumors that had positive margins or involvement of the seminal vesicles or lymph nodes. Within the latter group, however, there were 9 patients (11.3% of all 80 cases) with negative seminal vesicles and lymph nodes in whom excision of the neurovascular bundle at least reduced the extent of positive margins. Most of the positive margins in patients with tumor in the neurovascular bundle occurred outside the bundle region, and in this study, none of the cases with positive surgical margins were the sole result of failure to excise the neurovascular bundle. CONCLUSIONS: When perineural invasion is seen on needle biopsy, the morbidity of resecting one or both neurovascular bundles, which in some cases could turn out to be unnecessary, must be weighed against the benefit of reducing the incidence of positive margins (17.5% of our cases) or decreasing the extent of positive margins (11.3% of our cases).
Biopsy, Needle↗
Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings.
OBJECTIVES: Prostate cancer is rarely diagnosed in men younger than 40 years of age. It is thought, although not documented, that these tumors behave particularly aggressively. METHODS: We studied 87 men younger than 40 years old who underwent prostate needle biopsy and were from three populations: (a) 71 cases (63 benign, 7 cancer) from Dianon Systems; (b) 9 needle biopsies with cancer sent to one of us (J.I.E.) in consultation; and (c) 7 men with cancer who came to Johns Hopkins for consultation. RESULTS: The median age of men with a benign biopsy was 35 years (mean 33.9, range 22 to 39); the median age of men with cancer was 38 years (mean 35.9, range 22 to 39) (P = 0.004). The most common indications for biopsy were abnormal digital rectal examination (DRE) (n = 61); elevated prostate-specific antigen (PSA) (n = 14), and inflammatory symptoms (n = 12). Other reasons cited included hematuria, abnormal ultrasound, pain, ejaculatory problems, obstructive symptoms, and family history of prostate cancer. The median PSA was 2.6 ng/mL (mean 4.8, range 0.3 to 66) for all men, 1.2 ng/mL (mean 3.4, range 0.3 to 19.9) for benign cases, and 4.4 ng/mL (mean 8.7, range 2.1 to 66) for cancer (P = 0.0004). Abnormal DRE was not predictive of cancer. Of the 55 patients whose family history was known, 40 men had no family history of prostate cancer, and of those, only 6 (15%) had cancer. Of the 1 5 patients with a family history of cancer, 6 (40%) were found to have cancer on biopsy (P = 0.05). Of the 23 patients with cancer, 3 were lost to follow-up, 1 was treated with hormones, and 3 chose watchful waiting. The remaining 16 patients underwent radical prostatectomy and had diverse pathologic findings. Tumor volume ranged from 0.01 to 6.35 cc. Pathologic stage was pT2 in 9 cases and pT3 in 7 cases (2 with positive pelvic lymph nodes). In 14 men, serum PSA values were available: of 4 men with PSA greater than 10 ng/mL, all had Stage pT3, and of 10 men with PSA less than 10 ng/mL, 3 had Stage pT3. CONCLUSIONS: Young men who are candidates for radical prostatectomy have potentially curable disease, particularly if PSA at the time of diagnosis is less than 10 ng/mL.
Adenocarcinoma↗
Prostate cancer sampled on sextant needle biopsy: significance of cancer on multiple cores from different areas of the prostate.
OBJECTIVES: To determine the relationship between the location of positive sites, when more than one sextant site shows prostate cancer in a given patient, and pathologic stage, tumor volume, and margin status if radical prostatectomy is performed. METHODS: We performed biopsies using a spring-loaded biopsy gun on 343 Stage T1c (nonpalpable) radical prostatectomy specimens from each sextant site. RESULTS: In 56 cases, carcinoma was identified in two separate sextant sites. In 38 cases, the sites were vertical to each other (ie, left apex, left mid); in 8 cases, the sites were diagonal (ie, left apex, right mid); in 5 cases, the sites were horizontal (ie, left apex, right apex); and in 5 cases, they were not contiguous but were separated by an uninvolved sextant site (ie, left apex, left base). Tumors were more likely to be multifocal in cases with diagonally positive biopsies (P <0.0001) and horizontally positive biopsies (P <0.0001) than in those with vertically positive biopsies. No significant differences were found in organ-confined status and margin positivity among cases with different positive biopsy locations. The dominant tumor nodule was larger (mean 2.76 cc) in cases with noncontiguously positive biopsies than in all other groups combined (mean 1.44 cc) (P = 0.017). CONCLUSIONS: When more than one sextant site shows cancer, there are differences in terms of whether the tumors sampled are multifocal versus solitary depending on which sites are positive. However, no significant differences were found in predicting pathologic stage and margin positivity.
Biopsy, Needle↗
Significance of small foci of Gleason score 7 or greater prostate cancer on needle biopsy.
OBJECTIVES: With increased screening for prostate cancer, we have noted a greater number of patients with small foci of Gleason score 7 or greater prostate cancer on needle biopsy. The significance of these findings is unknown. METHODS: We studied 57 men with small foci of Gleason score 7 or greater on needle biopsy. Tumor length was less than 1.5 mm in all but 2 cases. In those 2 cases, there were two minute (less than 0.5 mm) foci of cancer separated by 1.8 mm. The length of cancer ranged from 0.2 to 1.8 mm (mean 0.63 mm). In all cases, only one core was involved. RESULTS: Thirty-three men underwent radical prostatectomy (RP), 14 received radiation, 8 underwent surveillance, and 2 received hormonal therapy. Men who underwent RP were younger (62 years) than those who had radiotherapy (69.1 years), who were younger than those who underwent surveillance (74.5 years). The mean prostate-specific antigen (PSA) for men undergoing RP was 8.0 ng/mL (range 1.4 to 22). Preoperative serum PSA values did not predict organ-confined status. Needle biopsy grades were as follows: 3 + 4 = 7 (n = 30); 4 + 3 = 7 (n = 17); 4 + 4 = 8 (n = 7); 5 + 4 = 9 (n = 1); and 5 + 5 = 10 (n = 2). We were able to review slides in 27 of the RP specimens, of which 24 were well sampled. Of these 24 cases, 33% had positive margins and 33% were not organ confined; the median tumor volume was 0.5 cc (mean 1.04). No difference in RP tumor volume was found between tumors with needle biopsy Gleason primary grade 3 and those with 4 or greater. The percentage of Gleason pattern 4 on needle biopsy weakly correlated with the percentage of Gleason pattern 4 in the RP specimen (P = 0.04). However, the percentage of Gleason pattern 4 only in the RP specimen, but not in the biopsy, correlated with whether the tumor was organ confined. CONCLUSIONS: The likelihood of having organ-confined disease with small foci of Gleason score 7 or greater on needle biopsy appears to be equivalent to that calculated from the Partin Tables for greater amounts of Gleason score 6 cancer on needle biopsy. In men who are considering RP, small foci of Gleason score 7 or greater adenocarcinoma on needle biopsy should not necessarily be considered an adverse finding.
Aged↗
Nuclear shape and nuclear matrix protein composition in prostate and seminal vesicles.
OBJECTIVES: The nucleus controls cell function and behavior. The nuclear matrix determines internal nuclear changes. Two-dimensional gel electrophoresis is the reference standard for the analysis of nuclear matrix protein (NMP) composition. Differences in NMP composition should therefore be reflected by changes in nuclear shape. We investigated the differences in NMP composition and nuclear morphometry of the prostate and seminal vesicles. Both tissues are androgen-dependent sex accessory organs with completely different biologic behavior. METHODS: High-resolution two-dimensional gel electrophoresis and silver staining were used to evaluate NMP composition from histologically normal prostate and seminal vesicle epithelial cells. Nuclear morphometry, performed using a computer-assisted image analysis system, described the distribution, variability, and extremes of nuclear shape. RESULTS: NMP composition analysis demonstrated that both tissues have a similar NMP composition, and tissue-specific NMPs that were consistently present in all specimens of each tissue could not be demonstrated. Nuclear morphometry showed a significantly greater heterogeneity in nuclear shape in the seminal vesicles than in the prostate. CONCLUSIONS: The striking similarity of the NMP composition demonstrates the close biologic relationship between prostate and seminal vesicle tissue. The similar NMP composition does not correlate with the marked alterations in nuclear shape and structure between these tissues. Therefore, nuclear morphometry may depict differences in the functional state of a similar set of NMPs, shown by two-dimensional gel electrophoresis, which may be responsible for the different biologic behavior of these tissues.
Antigens, Nuclear↗
Genetically engineered neural networks for predicting prostate cancer progression after radical prostatectomy.
OBJECTIVES: To use pathologic, morphometric, DNA ploidy, and clinical data to develop and test a genetically engineered neural network (GENN) for the prediction of biochemical (prostate-specific antigen [PSA]) progression after radical prostatectomy in a select group of men with clinically localized prostate cancer. METHODS: Two hundred fourteen men who underwent anatomic radical retropubic prostatectomy for clinically localized prostate cancer were selected on the basis of adequate follow-up, pathologic criteria indicating an intermediate risk of progression, and availability of archival tissue. The median age was 58.9 years (range 40 to 87). Men with Gleason score 5 to 7 and clinical Stage T1b-T2c tumors were included. Follow-up was a median of 9.5 years. Three GENNs were developed using pathologic findings (Gleason score, extraprostatic extension, surgical margin status), age, quantitative nuclear grade (QNG), and DNA ploidy. These networks were developed using three randomly selected training (n = 136) and testing (n = 35) sets. Different variable subsets were compared for the ability to maximize prediction of progression. Both standard logistic regression and Cox regression analyses were used concurrently to calculate progression risk. RESULTS: Biochemical (PSA) progression occurred in 84 men (40%), with a median time to progression of 48 months (range 1 to 168). GENN models were trained using inputs consisting of (a) pathologic features and patient age; (b) QNG and DNA ploidy; and (c) all variables combined. These GENN models achieved an average accuracy of 74.4%, 63.1 %, and 73.5%, respectively, for the prediction of progression in the training sets. In the testing sets, the three GENN models had an accuracy of 74.3%, 80.0%, and 78.1%, respectively. CONCLUSIONS: The GENN models developed show promise in predicting progression in select groups of men after radical prostatectomy. Neural networks using QNG and DNA ploidy as input variables performed as well as networks using Gleason score and staging information. All GENN models were superior to logistic regression modeling and to Cox regression analysis in prediction of PSA progression. The development of models using improved input variables and imaging systems in larger, well-characterized patient groups with long-term follow-up is ongoing.
Adult↗
Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study.
The human prostate and seminal vesicles are both androgen-dependent sex accessory organs. Their growth behavior, response to hormone manipulation, susceptibility to benign and malignant processes and sex accessory functions, however, differ greatly. The growth behavior of most tissues correlates well with the cell turnover rate of that tissue. Therefore, we compared the cell turnover of normal human prostate and seminal vesicles. Immunohistochemical expression of MIB-1 (proliferation), bcl-2 and transforming growth factor (TGF beta) were examined in 20 different samples taken from histologically normal human prostatic and seminal vesicle tissue. For the quantification of apoptosis, the TUNEL technique was used. The apoptosis rates in normal prostatic tissue (0.73+/-0.60) were significantly greater (P=0.003) than those seen in seminal vesicles (0.02+/-0.01). The proliferation rates also differed significantly (P=0.002) between these tissues (prostate: 0.77+/-0.78; seminal vesicles: 0.02+/-0.02). Eighty percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the prostate samples stained for TGF beta. For both androgen-dependent tissues, apoptotic rates closely equaled proliferation rates. The cell turnover, however, was much higher in the prostate than in the seminal vesicles. TGF beta seems to be more important for the regulation of cell turnover in the seminal vesicles than bcl-2. These differences in the proliferative behavior may explain why disturbances of apoptotic regulation lead to a more extensive net cell gain in prostatic tissue compared to the seminal vesicles. This might help explain the vastly different incidence of benign and malignant tumors in these organs.
Journal Article↗
Can immunohistochemistry enhance the detection of micrometastases in pelvic lymph nodes from patients with high-grade urothelial carcinoma of the bladder?
Immunohistochemistry for keratin has enhanced our ability to detect micrometastases in certain cancer patients with negative lymph nodes by routine histologic examination of H&E-stained sections. However, there is no information about micrometastasis of bladder cancer. We performed immunohistochemistry for keratins on 159 pelvic lymph nodes, which were negative for metastatic tumors on routine H&E-stained sections, from 19 patients with high-grade muscle invasive urothelial bladder cancer. In 1 man, 1 lymph node contained a keratin-positive micrometastasis that was not present on the original H&E-stained slide. However, the metastasis was seen readily on a new H&E-stained section prepared from the paraffin block adjacent to the keratin-stained section. Immunohistochemical analysis for keratins revealed no additional case of micrometastasis of urothelial carcinoma of the bladder. The perinodal fibroadipose tissue of a lymph node from a woman contained a few keratin-positive benign glands of endosalpingiosis. A thorough examination of the H&E-stained sections is the best method for detecting lymph node metastases of urothelial carcinoma from the bladder. There is a potential risk for misdiagnosis of metastases by using immunohistochemistry or polymerase chain reactions for keratins because of the occasional presence of benign epithelial cells in pelvic lymph nodes and associated connective tissue.
Adult↗
Rare expression of high-molecular-weight cytokeratin in adenocarcinoma of the prostate gland: a study of 100 cases of metastatic and locally advanced prostate cancer.
Immunohistochemistry with antibodies for high-molecular-weight cytokeratin labels basal cells and is used as an ancillary study in diagnosing prostate carcinoma, which reportedly lacks expression of high-molecular-weight cytokeratin. A recent report questioned the specificity of this marker, describing immunopositivity for high-molecular-weight cytokeratin in a small series of metastatic prostate cancer. We have also noted rare cases of prostate lesions on biopsy with typical histological features of adenocarcinoma showing immunopositivity for high-molecular-weight cytokeratin, either in tumor cells or in patchy cells with the morphology of basal cells. In some of these cases, it was difficult to distinguish cancer from out-pouching of high-grade prostatic intraepithelial neoplasia. To investigate whether prostate cancer cells express high-molecular-weight cytokeratin, we studied 100 cases of metastatic prostate carcinoma and 10 cases of prostate cancer invading the seminal vesicles from surgical specimens. Metastatic sites included regional lymph nodes (n = 67), bone (n = 19), and miscellaneous (n = 14). Cases with any positivity for high-molecular-weight cytokeratin antibody (34betaE12) were verified as being of prostatic origin with immunohistochemistry for prostate-specific antigen and prostate-specific acid phosphatase. Only four cases were detected positive for high-molecular-weight cytokeratin. In two cases (one metastasis, one seminal vesicle invasion) there was weakly diffuse positivity above background level. Two metastases in lymph nodes showed scattered strong staining of clusters of tumor cells, which represented <0.2% of tumor cells in the metastatic deposits. These positive cells did not have the morphology of basal cells. We conclude that prostate cancer, even high grade, only rarely expresses high-molecular-weight cytokeratin. This marker remains a very useful adjunct in the diagnosis of prostate cancer.
Acid Phosphatase↗
How often are diagnostic features missed with less extensive histologic sampling of prostate needle biopsy specimens?
The authors determined whether clinically relevant diagnostic information would be lost by examination of <3 levels per tissue core in prostate needle biopsy specimens. They evaluated 439 consecutive sextant biopsy specimens for the following three histopathologic features: presence of adenocarcinoma involving one core, Gleason pattern 4 in cases of grade 3 + 4 = 7 adenocarcinoma, and perineural invasion (PNI) by carcinoma. For all cases, 3 levels from each involved core were reviewed for the presence or absence of these three features. In 50 cases with adenocarcinoma involving only 1 core, diagnostic carcinoma was present on all 3 levels in 43 cores (86%). Carcinoma was present on only 2 levels in 3 cores (6%), present only on 1 level in 3 cores (6%), and present only on additional cut-downs, not on the original 3 levels in 1 core (2%). Among 32 cases, 51 cores were identified that contained Gleason grade 3 + 4 = 7 adenocarcinoma. In 41 cores (80%), pattern 4 was identified in all 3 levels. In 5 cores (10%), pattern 4 was identified on only 2 levels, and in another 5 cores (10%), pattern 4 was present on only 1 level. Among 36 cases, 69 tissue cores were identified that contained perineural invasion (PNI). In 54 cores (78%), PNI was present on all 3 levels. In 7 cores (10%), PNI was present on only 2 of 3 levels, while in 7 other cores (10%), PNI was present on only 1 of 3 levels. In 1 core (1.5%), PNI was noted only on additional cutdowns, not on the original 3 levels. We estimated that reducing the number of levels to 1 per core could result in the misdiagnosis of PNI, grading, or carcinoma in approximately 8-11% of cores with these features and could have changed the case diagnosis in 9 of 439 cases. If only 2 levels were reviewed, we predict misdiagnosis in 5% to 6% of cores with these features and a change in the case diagnosis in 5 of 439 cases. Misdiagnosis of clinically relevant features on prostate biopsy specimens can be minimized with histologic review of 3 levels per tissue core.
Adenocarcinoma↗