Epidermal dynamics and patterns of intraepidermal melanoma.

BACKGROUND: Dermatopathologists know that the epidermis represents a dynamic compartment and that its cells mature from the basal layer to the skin surface in approximately 45 days. What may seem intuitive - but not obvious - is that the dynamics of the epidermis can affect the patterns of melanoma cells within the epidermis. Here this conjecture is explored with an abstract, theoretical model. METHODS: To control the independent effects of epidermal replacement velocity and thickness as well as rate of melanoma cell penetration of the epidermis, an abstraction of the epidermis was created and simulated via computer. RESULTS: Simulated plots of the epidermis show that the number and pattern of melanoma cells in the epidermis is affected by the probability of melanoma cells entering the epidermis, by the velocity of epidermal replacement and by epidermal thickness. CONCLUSION: This analysis suggests that the dynamics of the epidermis are sufficient to affect the patterns of melanoma cells within the epidermis.

Intratumoral inflammation is associated with more aggressive prostate cancer.

PURPOSE: Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease. METHODS: The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively. RESULTS: No inflammation was found in 49 men (17%), while 153 (53%) and 85 (30%) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44%) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95% CI 1.02-4.24), but not after adjusting for pathologic features. CONCLUSIONS: Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.

Dermatopathology of the foreskin: an institutional experience of over 400 cases.

BACKGROUND: Diseases of the foreskin may manifest with an array of pathologic findings, including potentially under-recognized dermatologic conditions. Herein, we summarize an institutional experience in foreskin dermatopathology. METHODS: Diagnoses rendered on foreskin specimens between 1982 and April 2009 were obtained through a computer-based keyword search. Cases given normal, non-specific or descriptive diagnoses were reviewed by a dermatopathologist. RESULTS: Keyword search yielded 414 foreskin diagnoses. Interpretations included normal foreskin (n = 131), benign lesions (n = 262) and malignant/dysplastic entities (n = 21). Of 353 cases given normal, descriptive or non-specific diagnoses, 334 were reviewed. Of reviewed cases, 209 (63%) were given more specific diagnoses [e.g. spongiotic dermatitis (n = 115), lichen sclerosus et atrophicus (LSA; n = 41), interface/lichenoid dermatitis (n = 26), psoriasiform dermatitis (n = 7)]. Discrepancy between the clinical and pathologic impression was frequently noted (n = 77). CONCLUSIONS: This study shows benign inflammatory lesions represent the most frequent foreskin pathology. When possible, specific diagnoses should be rendered, as accurate classification may be of clinical importance. There is an abundance of recent literature on the role of circumcision in disease prevention, and this topic is explored. We discuss the theoretical possibility that foreskin inflammation compromises the mucosal/epithelial barrier, thus playing a role in disease transmission.

The dynamics of death in melanoma.

BACKGROUND: Melanoma has been recently characterized as an over-diagnosed tumor, and some have suggested that the 'epidemic' in melanoma is spurious. Nevertheless, a fraction of melanoma patients continue to die of this tumor. For any tumor, the hazard function provides information about the timing and intensity of fatalities, and to examine the details of fatality in melanoma, herein the hazard functions for melanoma are derived and examined. METHODS: Data for this study came from the SEER data base, from AJCC data and from previously published studies of melanoma, and the hazard function was derived using the sum of two gamma functions and a nonlinear least-squares fitting algorithm. RESULTS: The derived hazard functions for melanoma peak at 1-3 years, a result that implies a form of rapidly evolving and fatal melanoma that is not consistently identified by routine prognostic factors. Yet in recent years the hazard function for all melanomas has declined suggesting that much of the epidemic in melanoma is due to non-fatal tumors. CONCLUSION: Analyses of the hazard functions in a large number of melanoma patients has uncovered details about the dynamics of death that otherwise are not apparent.

Extent of High-Grade Prostatic Adenocarcinoma in Multiparametric Magnetic Resonance Imaging-Targeted Biopsy Enhances Prediction of Pathologic Stage.

CONTEXT.­: Multiparametric magnetic resonance imaging (mpMRI) of prostate with targeted biopsy has enhanced detection of high-grade prostatic adenocarcinoma (HG PCa). However, utility of amount of HG PCa (Gleason pattern 4/5) in mpMRI-targeted biopsies versus standard 12-core biopsies in predicting adverse outcomes on radical prostatectomy (RP) is unknown. OBJECTIVE.­: To examine the utility of amount of HG PCa in mpMRI-targeted biopsies versus standard 12-core biopsies in predicting adverse RP outcomes. DESIGN.­: We performed a retrospective review of prostate biopsies that had corresponding RP, 1 or more mpMRI-targeted biopsy, and Grade Group 2 disease or higher. For the 169 cases identified, total millimeters of carcinoma and HG PCa and longest length HG PCa in a single core were recorded for 12-core biopsies and each set of mpMRI-targeted biopsies. For RP specimens, Gleason grade, extraprostatic extension, seminal vesicle involvement, and lymph node metastasis were recorded. The main outcome studied was prostate-confined disease at RP. A logistic regression model was used to test which pre-RP variables related to this outcome. RESULTS.­: Univariate analysis showed significant associations with adverse RP outcomes in 5 of 8 quantifiable variables; longest millimeter HG PCa in a single 12-core biopsy, highest Grade Group in any core, and total millimeter HG in mpMRI-targeted biopsies showed no statistical association (P = .54, P = .13, and P = .55, respectively). In multivariate analysis, total millimeter carcinoma in all cores, highest Grade Group in any core, and longest millimeter HG PCa in a single mpMRI-targeted core provided additional predictive value (P < .001, P = .004, and P = .03, respectively). CONCLUSIONS.­: Quantitation of HG PCa in mpMRI-targeted biopsies provides additional value over 12-core biopsies alone in predicting nonorgan confined prostate cancer at RP. Linear millimeters of HG PCa in mpMRI-targeted biopsies is a significant parameter associated with higher pathologic stage and could be of value in risk models.

PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer.

OBJECTIVE: To investigate the interaction between, and significance of, ERG gene rearrangements and PTEN genomic deletions in relation to the development and progression of prostate cancer (PCA). PATIENTS AND METHODS: We interrogated an initial cohort of 220 men with localized PCA using fluorescence in situ hybridization for ERG rearrangements and PTEN genomic deletions. RESULTS: The incidences of ERG rearrangements and PTEN deletions in PCA were significantly higher than in high-grade prostatic intra-epithelial neoplasia (HGPIN) and benign prostate tissue (P < 0.001). ERG rearrangements and PTEN deletions were detected in 41.9 and 42.6% of patients' tumours, respectively. ERG rearrangements were never detected in benign prostate tissue, while PTEN aberrations were present at a basal level of 4.6%. PTEN hemizygous deletions showed higher frequency than homozygous deletions within each diagnostic category from benign prostate tissue to HGPIN and PCA (P ≤ 0.001). Furthermore, in 29 patients where all three tissues were available, PTEN genomic aberrations in PCA were significantly different from those in benign tissue (P = 0.005) and HGPIN (P = 0.02), reflecting the accumulation of genomic aberrations in the early stages of disease progression. Within this cohort, 71.4% of homozygous and 44.2% of hemizygous PTEN deletions occurred simultaneously with ERG rearrangements (P ≈ 0). Stratified according to Gleason score (GS), hemizygous PTEN deletions across various GS groups were observed at a higher frequency than homozygous deletions. However, PTEN homozygous deletions showed positive trends with higher GS, increasing in poorly differentiated PCA (GS 8-10) in comparison to moderately and well differentiated tumours (GS 6 and 7). CONCLUSION: We show significant association between ERG gene rearrangements and PTEN genomic aberrations in subset of PCA. Our analysis also provides further support for the observation that homozygous PTEN deletions can occur within the subset of HGPIN lesions, and shows accumulating genetic aberrations with disease progression, evidenced by higher detection in PCA than in HGPIN and more PTEN homozygous deletions in GS 8-10 than in 6-7.

Osteosarcoma after radiotherapy for prostate cancer.

Postradiation sarcomas are long-term complications of radiation treatment of various forms of cancer. Osteosarcoma, specifically, occurring in patients with a history of prostate cancer is rare; but with high-dose radiotherapy now an accepted standard of care for localized prostate adenocarcinoma, it should be considered in the clinical setting of patients presenting with potential remote disease relapse. We describe an osteosarcoma of the pubic ramus in a patient previously treated 10 years prior with radiation therapy for prostate cancer. Because of the long latency period, the appearance of lytic bone lesions with soft tissue components in pelvic bony structures may mimic recurrent/metastatic prostate adenocarcinoma. The prognosis of patients developing osteosarcoma after radiotherapy for prostate cancer is similar to other radiation-induced osteosarcomas occurring in the axial skeleton, with a 50% overall mortality within the first year after diagnosis.

Sarcomatoid mesothelioma: a clinical-pathologic correlation of 326 cases.

Sarcomatoid mesothelioma is the least common, but most aggressive of the three major histological types of mesotheliomas. This study comprises 326 cases of sarcomatoid mesotheliomas among 2000 consecutive malignant mesothelioma cases received in consultation (16%). Patients included 312 men (96%) and 14 women (4%), with a median age of 70 years (range 41-94 years). Most tumors were pleural (319; 98%), and 7 were peritoneal (2%). Some desmoplastic features were identified in 110 cases (34%), and 70 (21%) were classified as desmoplastic. Rare subtypes included two cases with a lymphohistiocytoid pattern (<1%) and eight heterologous mesotheliomas (2%). Labeling for cytokeratins (CKs) was observed in 261/280 cases (93%), and for calretinin and vimentin in 31 and 91%, respectively. Pleural plaques were present in 79% of cases for which information was available, and asbestosis was diagnosed in 34/127 cases (27%). Median survival was 3.5 months. Fiber analysis was performed in 61 cases. The median asbestos body count was 1640/g wet lung tissue (by light microscopy). Amosite fibers were the most commonly identified fibers using energy-dispersive X-ray analysis and were significantly higher in the sarcomatoid cases, as were uncoated fibers using scanning electron microscopy. This study represents the largest series of sarcomatoid and desmoplastic malignant mesotheliomas to date and confirms the diagnostic usefulness of CK immunohistochemistry. The relationship with asbestos exposure--particularly amosite--and an association with pleural plaques and less often asbestosis is confirmed.

Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma.

Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 stimulates cell proliferation. In this study, we characterized the pattern of expression of GRP78 and MTJ1 in invasive primary cutaneous melanomas and analyzed the relationships between the pattern of expression and various clinicopathological parameters. We found two patterns of GRP78 expression in invasive primary cutaneous melanoma. One pattern showed a gradual fading of protein expression from superficial to deeper levels within the same tumor. The second pattern of expression showed a similar fading with an abrupt regaining of expression at the deep invasive edge of the melanoma. These two distinct patterns of GRP78 expression correlated with both patient survival and depth of tumor invasion. A moderate MTJ1 expression was found to be associated with decreased patient survival; however, no significant associations were observed between patterns of GRP78 and MTJ1 expression. Our study (1) describes two distinct patterns of GRP78 in invasive primary cutaneous melanoma, (2) inversely correlates regain of GRP78 expression with patient survival, and (3) suggests a modifying effect of MTJ1 on GRP78 in enhancing tumor aggressiveness.

Syndecan-1 expression in prostate cancer and its value as biomarker for disease progression.

OBJECTIVE: To evaluate the association between syndecan-1 (CD138) expression and prostate cancer. PATIENTS AND METHODS: We evaluated syndecan-1 expression using a recently constructed tissue microarray of prostatic samples taken from 243 patients, corresponding to 1400 cores, with 69.8%, 5.6%, 17.6% and 7% of the cores representing localized prostate cancer, high-grade prostatic intraepithelial neoplasia, benign prostate tissue and hormone refractory/metastatic disease, respectively. RESULTS: Metastatic cases had the highest frequency and membranous staining intensity for syndecan-1 overexpression, followed by hormone refractory and localized disease (83.3% vs 34.8% and 25.7%, respectively). There was no significant difference in the frequency of membranous syndecan-1 expression between localized prostate cancer and benign glands (25.7% vs 24.7% of cases, respectively). However, benign glands showed significantly higher intensity staining than localized prostate cancer. We found no significant association between syndecan-1 expression and any of the following: Gleason score, pathological stage, surgical margin status and biochemical recurrence. CONCLUSION: The current available evidence, from the present and previous studies, show that syndecan-1 is not an independent predictor of recurrence or tumour-specific survival, diminishing its significance as a clinical marker.

Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

Fascin regulates prostate cancer cell invasion and is associated with metastasis and biochemical failure in prostate cancer.

PURPOSE: Prostate cancer metastasis to secondary organs is considered an initial event in the development of hormone refractory disease and remains the major cause of death among prostate cancer patients. In this study, we investigated the role of fascin, a cytoskeleton actin-bundling protein involved in the formation of filopodia and cell migration, in prostate cancer progression. EXPERIMENTAL DESIGN: Fascin protein expression was examined by immunohistochemistry in a cohort of 196 patients with localized prostate cancer and across several stages of disease progression, including hormone refractory disease. Cellular changes were also assessed in vitro and in vivo in DU145 prostate cancer cell line using fascin gene silencing. RESULTS: Fascin epithelial expression was significantly up-regulated in localized and hormone refractory prostate cancer compared with benign prostate tissue (P<0.05). Furthermore, high fascin expression was associated with an increased rate of prostate-specific antigen recurrence following radical prostatectomy (P=0.075), signifying more aggressive clinical course, thus supporting a function for fascin in prostate cancer progression. In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties. In addition, fascin small interfering RNA-expressing DU145 cells implanted orthotopically in mouse prostate showed significantly decreased growth (P<0.005) and drastically prevented the formation of lymph node metastases (P<0.001) compared with their matched controls. CONCLUSIONS: Our data show a function of fascin in the regulation of prostate cancer progression and emphasize the importance of fascin as a prognostic marker for aggressive disease and as a potential therapeutic target for advanced androgen independent disease.

The Importance of Tumor Length in Needle Biopsies of the Prostate.

OBJECTIVES: To form a composite predictor variable that combines the effects of tumor length, serum prostate-specific antigen (PSA), and International Society of Urologic Pathologists (ISUP) grade on the observation of adverse prostatectomy pathology. METHODS: Logistic regression analysis was used to demonstrate how tumor length, serum PSA, and ISUP grade related to adverse prostatectomy results and to derive weighting factors for a composite variable, cx. RESULTS: The composite variable, cx, relates closely to adverse prostatectomy results as well as to observed PSA failure. CONCLUSIONS: The composite variable cx uses preoperative information that may allow the sorting of patients into low, intermediate, and high risk for adverse outcomes after prostatectomy.

Personalized prediction of tumor response and cancer progression on prostate needle biopsy.

PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.

p16 Improves interobserver agreement in diagnosis of anal intraepithelial neoplasia.

OBJECTIVES: Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (H&E) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement. MATERIALS AND METHODS: Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed H&E alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics. RESULTS: Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using H&E diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for H&E/p16/Ki-67 combined were comparable to that of H&E alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, H&E/p16/Ki-67 combined, and H&E alone. CONCLUSIONS: Interobserver agreement for diagnosis of AIN was fair when based solely on H&E preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with H&E, Ki-67, and H&E/p16/Ki-67 combined.

A review of the incidence of adenocarcinoma detected during surveillance for Barrett's esophagus.

The objective of this study is to provide an up-to-date estimate of the incidence of adenocarcinoma detected during surveillance of Barrett's esophagus. Fifty-five longitudinal studies involving approximately 61 000 patients were reviewed. A general linear model analyses with Poisson link function was used to study how the number of cancer cases detected depended on study details. The studies seemed to follow the same statistical model, and the probability of developing Barrett's carcinoma during surveillance was found to depend on the following variables: how Barrett's metaplasia was defined, the number of patients studied, the mean time of follow-up, and the fraction of patients followed up for at least 5 years. The model derived from all the studies predicted that the per-person probability of developing cancer in 5 years of complete follow-up is approximately .0012.

The Calculus of Serum PSA.

OBJECTIVES: To review the mathematics of kinetic changes in serum prostate-specific antigen (PSA) and to use a compartmental model to derive a new kinetic measure, alpha. METHODS: The calculus of kinetic measures of PSA changes with time is presented, and a compartmental model is then used to derive alpha of serum PSA. Alpha is then tested for prognostic importance in 119 men who underwent prostatectomy. RESULTS: The percentage of tumor in the prostate is closely related to alpha and to tumor length in diagnostic needle biopsies, but not to tumor grade. The presence of adverse pathology in the prostatectomy specimens (positive margins or T3 stage) is significantly associated with alpha, but not to tumor length or grade. CONCLUSIONS: The derived kinetic parameter, alpha, shows promise as a preoperative prognostic parameter, and may help sort patients into those with low vs high probability for adverse pathology features in the prostatectomy specimens.

Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery.

BACKGROUND: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. METHODS: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (<20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and low-density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. RESULTS: Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67-positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) versus 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serologic endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P = 0.048). CONCLUSIONS: Findings suggest that flaxseed is safe and associated with biological alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.

Twenty-five years of fiber analysis: what have we learned?

Asbestos exposure has resulted in a variety of diseases, including asbestosis, carcinoma of the lung (LC), pleural plaques, and malignant mesothelioma (MM). We hypothesized that there have been significant changes in the mineral fiber content of lung tissue from individuals with these diseases over the past 25 years. Asbestos content was measured in lung tissue samples from 819 individuals using light microscopy (to measure asbestos body concentrations) and scanning electron microscopy (to measure types and concentrations of mineral fibers). Cases were divided chronologically according to those occurring in the first half (group 1) versus those occurring in the second half (group 2). The study included 419 cases of MM, 206 cases of asbestosis, and 340 cases of LC. The median asbestos body count (in asbestos bodies per gram) decreased from group 1 to group 2 for each disease: MM, 480 to 350; asbestosis, 24700 to 19200; and LC, 1600 to 174 (reference range, 0-20). A similar trend was observed for fiber counts by scanning electron microscopy. Amosite was the most frequently detected asbestos fiber type and decreased in frequency of detection and median concentration from group 1 to group 2. Crocidolite showed an increased detection frequency from group 1 to group 2 across all 3 disease categories. The decrease in asbestos body and amosite concentrations over time is consistent with the banning of asbestos from insulation products in 1972. The source for the increased detection of crocidolite was not identified and needs further investigation.

Tumor length in prostate cancer.

To evaluate the impact of tumor length and fraction of positive biopsy cores on overall survival, I used the data for 526 patients with prostate cancer. Median follow-up in patients not observed until death was more than 6 years. In a Cox model analysis that included age, serum prostate-specific antigen (PSA) level, grade, and fraction of positive cores, tumor length was the most closely associated with overall survival time (P=6 x 10(-5)); however, the impact of tumor length was mostly for a subset of men with tumors measuring more than 20 mm. Patient age, serum PSA level, Gleason score, fraction of cores with tumor, and tumor length were all significantly codependent variables. For routine cases of prostate cancer, measuring tumor length in the needle cores may be unnecessary. Tumor length may assist studies of long-term outcomes or treatment trials in prostate cancer by reducing baseline variance better than other prognostic variables. For the few patients with unusually large amounts of tumor in biopsy specimens, tumor length may provide a concise indicator for the likelihood of an adverse outcome, especially when the values of other prognostic variables appear by themselves to be less ominous.