PubMed Health⌕ Search

Biomedical subjects

K A Iczkowski

Publications and source records attributed to K A Iczkowski.

33 records · Page 2Linked to original sources
PubMed1998

Malignant lymphoma involving the prostate: report of 62 cases.

BACKGROUND: Malignant lymphoma involving the prostate is rare, and to the authors' knowledge the factors determining patient outcome have not been studied in a large series. METHODS: The authors evaluated the clinical and pathologic findings in 60 cases of non-Hodgkin's lymphoma and 2 cases of Hodgkin's lymphoma involving the prostate. A variety of clinical and histologic findings were considered as factors predictive of patient outcome. RESULTS: Lymphoma tended to occur in elderly men, with a mean age at diagnosis of 62 years (range, 5-89 years), although 6 patients were age < 40 years (ages 5, 19, 30, 32, 38, and 38 years, respectively). Clinical signs and symptoms were due to lower urinary tract obstruction. Twenty-two patients (35%) presented with primary extranodal lymphoma of the prostate with a variety of histologic subtypes, including small lymphocytic (4 patients); follicular center cell, diffuse, small cell (2 patients); follicular center cell, Grade 1 (according to the revised European-American classification (small cleaved) (1 patient); Grade 2 (mixed) (1 patient); diffuse large B-cell (12 patients); and high grade B-cell lymphoma, Burkitt-like (2 patients). At the time of presentation, none of these patients had hepatosplenomegaly, inguinal lymphadenopathy, or an abnormal complete blood count. Thirty other patients (48%) with previously documented lymphoma at other sites developed prostatic involvement; these secondary prostatic lymphomas displayed a variety of subtypes, including small lymphocytic (8 patients, all with concomitant leukemia); follicular center cell lymphoma, diffuse, small cell (2 patients); follicular center, Grade 1 (small cell) (1 patient); follicular center, Grade 2 (1 patient); diffuse large B-cell (11 patients); peripheral T-cell lymphoma (2 patients); high grade B-cell lymphoma, Burkitt-like (1 patient); Burkitt's lymphoma (1 patient); Hodgkin's lymphoma (nodular sclerosing [1 patient] and mixed cellularity [1 patient]); and unknown (1 patient). Ten cases were not classifiable as primary or secondary lymphomas. Twenty-five patients died of malignant lymphoma, 14 died of unknown or other causes, 18 patients were alive 12-20 months after diagnosis (8 primary and 10 secondary tumors; 3 had persistent lymphoma; all treated since 1981), and 5 were lost to follow-up. Lymphoma specific survival was 64% at 1 year (95% confidence interval [CI], 51-80%), 50% at 2 years (95% CI, 36-68%), 33% at 5 years, 33% at 10 years, and 16% at 15 years. There was no difference in median survival after diagnosis of prostatic involvement between primary and secondary lymphoma (23 months vs. 28 months, respectively) or among histologic types. CONCLUSIONS: Although malignant lymphoma involving the prostate is rare, it should be considered in the differential diagnosis of lower urinary tract obstruction, particularly in patients with a previous history of lymphoma.

Adult↗
PubMed1998

Expression of early growth response genes in human prostate cancer.

Early growth-response (EGR) genes are nuclear transcription factors that are implicated in regulating cell proliferation. Because these genes show divergent expression in various human tumors, we sought to determine their expression in nonmalignant and malignant prostate tissues. Total RNA extracted from prostate tissues was probed with EGR-1, EGR-2, and EGR-alpha cDNA for Northern blots and digoxigenin-labeled cRNA for in situ hybridization. Both Northern blot and in situ hybridization analyses demonstrated increased EGR-1, but not EGR-2 or EGR-alpha expression, in malignant prostate tissue as compared with weak expression in nonmalignant tissue. EGR-1 mRNA was quantified in 96 prostate specimens (86 adenocarcinomas representing different Gleason scores and 10 benign tissues showing no histological manifestation of benign prostatic hypertrophy) using in situ hybridization with an 35S-labeled cRNA probe. EGR-1 mRNA was expressed at significantly higher levels in cancer than in normal prostate (P < 0.001). In cancer with Gleason scores 8-10, the expression of EGR-1 was higher compared with those of lower Gleason scores (P < 0.005). Immunohistochemical staining showed predominately basal cell nuclear EGR-1 protein in prostatic acini. Nuclear staining was weak in nonmalignant tissues, more intense in moderately differentiated carcinoma, and most intense in poorly differentiated carcinoma. These results show that EGR-1 is overexpressed in prostate cancer and suggest a role for EGR-1 in prostate cancer growth.

Adenocarcinoma↗
PubMed1998

Diagnosis of "suspicious for malignancy" in prostate biopsies: predictive value for cancer.

OBJECTIVES: Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for but not diagnostic of malignancy. The predictive value of ASAP for cancer has not been studied in a large series. METHODS: To determine the reproducibility and clinical significance of ASAP in a large urologic reference laboratory, we retrospectively studied 295 patients with ASAP diagnosed from 1991 to 1995. Each patient had at least one follow-up biopsy. Mean patient age was 68.0 years (range 40 to 89). Numerous clinical and histologic features were assessed to determine their predictive value for malignancy on subsequent biopsy. RESULTS: Adenocarcinoma was identified on follow-up biopsy in 125 patients (42%), with a median follow-up of 5.7 months (range 0.1 to 43). Gleason score varied from 4 to 9 (mean 6.2). Cumulative detection of 125 cancers was 90% after second biopsy and 99% after third biopsy. Serum prostate-specific antigen, digital rectal examination result, and patient age were not predictive of cancer on follow-up biopsy. Likewise, the number of biopsy cores and histologic findings including number of acini per focus of ASAP, number of foci of ASAP, degree of nuclear and nucleolar enlargement, and presence of luminal pink granular secretions, mucin, or crystalloids were not predictive of cancer. Stratifying our level of suspicion into three categories (favor benign, uncertain, and favor carcinoma) did not differentially predict subsequent cancer (44%, 44%, and 41% of patients, respectively; P = 0.86) nor the percentage of tissue involved by cancer. No clinical or pathologic feature affected the likelihood of subsequent cancer. In 39% of patients, cancer was only contralateral to or in a different sextant site from the initial ASAP site. CONCLUSIONS: The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. Sampling should include multiple sites in the prostate.

Adenocarcinoma↗
PubMed1998

Loss of CD44 variant 6 expression differentiates small cell carcinoma of urinary bladder from urothelial (transitional cell) carcinoma.

AIMS: Small cell carcinoma of the urinary bladder has a more aggressive biological potential than urothelial carcinoma, but its morphology may overlap with poorly differentiated urothelial carcinoma. The CD44 family of glycoproteins mediates cell-cell and cell-matrix adhesion. Aberrant regulation of expression of CD44, and particularly its v6 variant exon, has been correlated with aggressive or metastatic phenotype of some cancers. We measured the degree of protein expression of CD44v6 in small cell and urothelial bladder carcinoma. METHOD AND RESULTS: Immunohistochemical staining was performed with monoclonal antibodies against CD44v6. Immunoreactivity was absent in 25 of 27 cases of small cell carcinoma, with two showing only weak staining of fewer than 10% of cells. In contrast, all 12 cases of moderately or poorly differentiated urothelial carcinoma displayed moderately intense reactivity in 50% to 100% of cells. CONCLUSIONS: CD44v6 immunostaining discriminates cases of poorly differentiated urothelial carcinoma from small cell carcinoma. It also highlights the presence of mixed small cell urothelial differentiation when present.

Aged↗
PubMed1998

Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls.

The amount of non-cell-associated DNA free in blood plasma from pancreatic cancer patients usually exceeds that from healthy donors. We have evaluated the plasma DNA by gel electrophoresis and measured the variation in length of soluble DNA fragments by electron microscopy in plasma from three patients with pancreatic cancer and from three healthy controls. Whereas electrophoresis of nick-translated DNA isolated from plasma obtained from healthy controls showed autoradiographic bands at sizes equivalent to whole-number multiples (1-5x) of nucleosomal DNA (185-200 bp), in the samples obtained from pancreatic cancer patients, stronger ladder patterns appeared. Likewise, strand length distributions of DNA (DNA-SL) in the two groups differ. The DNA-SL distribution data include 2,752 measurements made from cancer patient plasma and 3,291 for control plasma. The shortest DNA-SL measured approximately 30 nm (approximately 88 bp calculated at 0.34 nm/bp) and the largest approximately 28,000 nm (>80,000 bp), with 50% of all lengths measuring between 100 and 900 nm long. The average plasma DNA-SL in controls (311 nm; median, 273 nm) exceeded that in cancer patients (231 nm; median, 185 nm). Small excesses of DNA at approximately 63, approximately 126, approximately 189, approximately 252, and approximately 315 nm, corresponding to small multiples of lengths associated with nucleosomes, were more prominent in the cancer patient plasma than in the healthy control plasma. This study provides evidence indicating differences in non-cell-associated DNA in plasma between cancer patients and healthy controls and indicates that a significant amount of this DNA is probably derived from apoptosis in neoplastic and/or normal cells.

Adult↗
PubMed1998

Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors.

We compared the expression of inhibin A, chromogranin, synaptophysin, S-100 protein, cytokeratins AE1/AE3, 7, and 20, and estrogen and progesterone receptors in testicular sex cord-stromal tumors: 11 Sertoli cell tumors, 3 Sertoli cell adenomas (nodules), 26 benign Leydig cell tumors, 7 malignant Leydig cell tumors (defined clinically by metastatic behavior), and a variety of germ cell tumors. Inhibin was the most sensitive marker, expressed in 91% of the Sertoli cell tumors and 100% of the Sertoli cell adenomas and Leydig cell tumors. The non-neoplastic Sertoli and Leydig cells invariably stained for inhibin. Conversely, no germ cell tumors were immunoreactive. One testicular tumor of the adrenogenital syndrome was immunoreactive. Neuroendocrine marker immunoreactivity was variable. Chromogranin was expressed in the non-neoplastic Sertoli and Leydig cells, 82% of the Sertoli cell tumors, 92% of the benign Leydig cell tumors, and 43% of the malignant Leydig cell tumors. Synaptophysin was expressed in the non-neoplastic Sertoli and Leydig cells, 45% of the Sertoll cell tumors, and 70% of the Leydig cell tumors, in approximately similar proportions between the benign and malignant Leydig cell tumors. S-100 protein was expressed in 64% of the Sertoli cell tumors, 8% of the benign Leydig cell tumors, and none of the malignant Leydig cell tumors. Cytokeratins AE1/AE3 were expressed in 64% of the Sertoli cell tumors and 42% of the Leydig cell tumors, with similar proportions in the benign and malignant cases. Estrogen and progesterone receptor expression were identified in 24 and 39% of benign and malignant Leydig cell tumors, respectively. We conclude that inhibin is a characteristic marker for Sertoli and Leydig cells and that it serves to differentiate testicular sex cord-stromal tumors from germ cell tumors.

Adolescent↗
PubMed1998

Microvessel density in prostate cancer: prognostic and therapeutic utility.

Microvessel density is a promising prognostic factor in management of patients with prostate cancer. Unlike cancer cell-based factors, microvessel density is a host stromal factor that has apparently limited heterogeneity within a cancer. Its predictive value for pathological stage has been demonstrated in most but not all reports. Further, recent studies reveal that microvessel density may be predictive of cancer recurrence and perhaps survival in some patients. Inhibition of angiogenesis may be an effective chemopreventive approach, particularly for men at high risk of prostate cancer. The patient described in the case study may benefit from microvessel density determination. Manual or computer-assisted counting of microvessels in the diagnostic needle biopsy specimen would provide a value that could be compared with published findings to predict pathological stage and outcome, particularly in combination with Gleason score and serum prostate-specific antigen concentration. The probability of extraprostatic extension may be sufficiently high that a urologist may choose not to operate on the patient. Similarly, the probability of recurrence after surgery or radiation may be sufficiently high to warrant adjuvant therapy.

Antineoplastic Agents↗
PubMed1997

Minimal criteria for the diagnosis of prostate cancer on needle biopsy.

Increased clinical screening of men at risk for prostate cancer, and the realization of the benefits of performing multiple biopsies per prostate, have facilitated early detection of malignancy, while presenting the pathologist with a growing array of diagnostic findings. Interpretation of these findings requires discussion of the minimal criteria required for the diagnosis of cancer on needle biopsy within a wide spectrum of related histologic findings. This spectrum includes small acinar proliferations suspicious for but not diagnostic of cancer, benign mimics of cancer, the preinvasive entity of high-grade prostatic intraepithelial neoplasia, and various treatment effects. Clinical implications of these findings and other prognostic factors are detailed.

Adenocarcinoma↗
PubMed1997

Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases.

Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for, but not diagnostic of, adenocarcinoma. The histologic features and clinical significance of this finding are unexplored. We evaluated 33 cases of ASAP with at least one follow-up needle biopsy seen at Mayo Clinic from 1993 to 1996. Numerous histologic and clinical features were assessed to determine their predictive value for adenocarcinoma on subsequent biopsy. Mean patient age was 61.6 years (range 45-72). Adenocarcinoma was identified on follow-up biopsy in 15 of 33 patients (45%), with a median follow-up of 9 months (range 1-27). Gleason score varied from 4 to 7 (mean 5.9). Two patients (6%) had subsequent diagnoses of ASAP after one and three repeat biopsies. Digital rectal examination, serum prostate-specific antigen, and a variety of histologic findings were not predictive of cancer on follow-up biopsy. These histologic findings included number of biopsy cores (mean 5.5), number of acini per focus of ASAP (mean 7.9), number of foci (mean one), variation in acinar size, nuclear enlargement (none, 12% of cases; mild, 45%; moderate, 33%; severe, 10%), nucleolar enlargement (none, 27%; mild, 46%; moderate, 27%), luminal mucin (39%), crystalloids (6%), focal chronic inflammation (64%), adjacent atrophy (100%), and adjacent high-grade prostatic intraepithelial neoplasia (PIN) (42%). Stratification of suspicion in cases of ASAP without PIN into three categories ("favor benign, uncertain, and favor carcinoma") was somewhat predictive of subsequent cancer (20%, 25%, and 60% of cases with subsequent cancer, respectively), but the results were not significant. The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. No single clinical or pathologic feature appeared to increase the likelihood of subsequent cancer.

Adenocarcinoma↗
PubMed1991

Morphometric study of the prepubertal rabbit testis: germ cell numbers and seminiferous tubule dimensions.

Testes from rabbits aged 1-9 weeks were examined by light microscopy. Changes in seminiferous tubule dimensions, testicular volume, and volume fraction of tubules were assessed. Germ cells and Sertoli cells were counted in round tubular cross sections and total germ cell number in each testis was estimated. Mitotic, meiotic, and degenerative activities of germ cells as well as their basal or central positions within tubules were quantified. A marked, steady increase in testis volume and in tubular length and volume occurred over the prepubertal period; but diameter underwent no significant increase and in fact decreased until week 4. Overall, tubules lengthened 40-fold and testis volume increased 25-fold; the percentage volume of the testis occupied by tubules rose from one-third neonatally to three-fifths at the onset of spermatogenesis. The ratio of germ cells to total tubular (germ and Sertoli) cells was lowest at 3 weeks. However, the total number of germ cells increased little until 3 weeks, after which it rose at a sharp rate commensurate with testis volume. Percentage of germ cells in mitosis peaked sharply at 3 weeks, dropped in subsequent weeks, and then rose at 7 weeks at the initiation of spermatogenesis. Importantly, the surge in mitosis at 3 weeks was followed by a redistribution of germ cells to a predominantly basal location from 3 to 7 weeks. Meiotic activity was sparse at 7 weeks and became abundant by 9 weeks. Germ cell degeneration remained relatively constant during weeks 1 through 6, with an increase at 7 weeks.

Animals↗
PubMed1991

Participation of the cytoskeleton in avian granulosa cell steroidogenesis.

Cytochalasin B (CB) and the more specific cytochalasin D (CD), disruptors of microfilament polymerization, and colchicine, an inhibitor of microtubule polymerization, were studied for their effects on cAMP and steroid production in granulosa cells of domestic fowl. Each agent was incubated with freshly dispersed cells from the largest preovulatory follicle of laying hens taken 3-4 hr before expected ovulation. Total content (cells + medium) of cAMP and steroids was measured by established radioimmunoassays. CB dose dependently inhibited basal as well as LH- and forskolin-stimulated cAMP generation and diminished basal, LH- and 25-hydroxycholesterol (25-OHC)-supported progesterone production. Conversely, CD potentiated LH- and forskolin-promoted cAMP generation as well as LH- and 25-OHC-stimulated progesterone synthesis. Neither drug had any influence on metabolism of pregnenolone to progesterone. Colchicine had no effect on cyclic AMP generation, yet it suppressed progesterone synthesis by inhibiting the conversion of pregnenolone to progesterone. beta-Lumicolchicine, a colchicine analog that does not depolymerize microtubules, had no such effect. The results suggest that microfilaments are involved in steroidogenesis at two sites, namely, the adenylate cyclase-cAMP system, and cholesterol conversion to pregnenolone; whereas microtubules act on the conversion of pregnenolone to progesterone.

Aminoglutethimide↗