Periprostatic adipose inflammation is associated with high-grade prostate cancer.

BACKGROUND: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown. METHODS: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry. Secondary objectives were to explore the clinical and systemic correlates of periprostatic WAT inflammation. Tumor characteristics and host factors including BMI, adipocyte diameter, and circulating levels of lipids, adipokines, and other metabolic factors were measured. Wilcoxon rank-sum, Chi-square, or Fisher's exact tests, and generalized linear regression were used to examine the association between WAT inflammation and tumor and host characteristics. RESULTS: Periprostatic fat was collected from 169 men (median age 62 years; median BMI 28.3). Periprostatic WAT inflammation was identified in 49.7% of patients and associated with higher BMI (P=0.02), larger adipocyte size (P=0.004) and Gleason grade groups IV/V tumors (P=0.02). The relationship between WAT inflammation and high Gleason grade remained significant after adjusting for BMI (P=0.04). WAT inflammation correlated with higher circulating levels of insulin, triglycerides, and leptin/adiponectin ratio, and lower high density lipoprotein cholesterol, compared to those without WAT inflammation (P's <0.05). CONCLUSION: Periprostatic WAT inflammation is common in this cohort of men with PC and is associated with high-grade PC.

Isolation and characterization of bacterial endophytes of Curcuma longa L.

Fourteen endophytic bacterial isolates were isolated from the rhizome of Curcuma longa L. were characterized on the basis of morphology, biochemical characteristics and 16S rRNA gene sequence analysis. The isolates were identified to six strains namely Bacillus cereus (ECL1), Bacillus thuringiensis (ECL2), Bacillus sp. (ECL3), Bacillus pumilis (ECL4), Pseudomonas putida (ECL5), and Clavibacter michiganensis (ECL6). All the strains produced IAA and solubilized phosphate and only two strains produced siderophore (ECL3 and ECL5) during plant growth promoting trait analysis. All the endophytic strains utilized glucose, sucrose and yeast extract as a carbon source where as glycine, alanine, cystine and glutamine as nitrogen source. The strains were mostly sensitive to antibiotic chloramphenicol followed by erythromycin while resistant to polymixin B. The endophytic strains effectively inhibit the growth of Escherichia coli, Klebsiella pneumoniae and some of the fungal strain like Fusarium solani and Alterneria alternata. The strain ECL2 and ECL4 tolerated maximum 8 % of NaCl concentration where as strains ECL5 and ECL6 6 % in salinity tolerance.

Substrate utilization of stress tolerant methylotrophs isolated from revegetated heavy metal polluted coalmine spoil.

We analyzed methylotrophs in Bina natural vegetation (BNV), and revegetated overburden dump of four (ROBD4) and 12 years (ROBD12), at Bina coal mine in Sonbhadra district. The cultured strains identified as Pseudomonas, Acinetobacter, Stenotrophomonas and Cellvibrio (γ-Proteobacteria), Methylophilus, Ralstonia, Burkholderia (α-Proteobacteria) Methylobacterium and Inquilinus (ß-Proteobacteria), Bacillus (Firmicutes) and Flexibacter (Sphingobacteria) in their 16s rRNA gene sequence similarity. The strains differed in citrate, lactose, formate, urea and xylose utilization. Methanol utilization by Stenotrophomonas, Inquilinus, Cellvibrio and Flexibacter is for first time. The preferred N- sources were proline, glutamate and nitrate for most of the strains. All strains tolerated (2.5 % NaCl) and SDS (0.2 %); 16 strains survived in crystal violet (0.01 %) and nine strains in sodium azide (0.02 %. Methylotrophic population trend was BNV > ROBD12 > ROBD4. The presence of majority of strain of BNV at ROBD12 and ROBD4 indicated restoration of soil methylotrophic functional diversity in revegetated dumps.

Cyanobacteria in Antarctica: ecology, physiology and cold adaptation.

Cyanobacterial species composition of fresh water and terrestrial ecosystems and chemical environment of water in Schirmacher Oasis in Continental Antarctica was investigated. Over 35 species of cyanobacteria were recorded. Diazotrophic species both heterocystous and unicellular contributed more than half to the count except in lake ecosystem. The species composition varied among the fresh water as well as terrestrial ecosystems. The physico-chemical analyses of water revealed its poor nurient content which might have supported the growth of diazotrophic cyanobacteria in an Antarctic environment. Among the cyanobacteria Oscillatoria, Phormidium and Nostoc commune were the dominant flora in most of the habitats. The physiological characteristics of isolated cyanobacteria strains indicated that N2-fixation, nitrate uptake, nitrate-reduction, ammonium-uptake, GS-transferase activity and photosynthesis was unaffected at low temperature (5 degrees C) which indicated low temperature adaptation for Antarctic cyanobacteria. This phenomenon was not evident in different strains of tropical origin. The temperature optima for N2-fixation for the different Antarctic cyanobacterial strains was in the range of 15-25 degrees C, nearly 10 degrees C lower than their respective reference strains of tropical origin. Similar results were obtained for cyanobacteria-moss association. The low endergonic activation energy exhibited by the above metabolic activities supported the view that cyanobacteria were adapted to Antarctic ecosystem.

Cytologic diagnosis of metastatic basal cell carcinoma. Report of a case with immunocytochemical and molecular pathologic considerations.

BACKGROUND: Metastases of basal cell carcinoma (BCC) are extraordinarily rare events, with only about 200 published reports. The usefulness of immunohistochemical markers in the diagnosis of metastatic BCC was previously established on cytologic material. Furthermore, in recent years, numerous molecular markers have been studied to explain its pathogenesis and relatively indolent behavior. CASE REPORT: A 62-year-old, white male presented with lymphadenopathy in the right side of the neck. The patient had a long-standing history of multiple excisions of BCCs during the previous 30 years. Fine needle aspiration biopsy revealed tight clusters and sheets of small, round tumor cells with hyperchromatic nuclei, small nucleoli and minimal cytoplasm. In addition, in some of the clusters the tumor cells showed peripheral palisading. Based on the cytomorphology and diffuse immunohistochemical positivity for a low-molecular-weight cytokeratin marker, MNF 116, and negativity for AE1/AE3, Cam5.2, synaptophysin and chromogranin, a diagnosis of metastatic BCC was rendered. Subsequent histopathologic examination of metastatically involved lymph nodes removed in a radical neck dissection confirmed this diagnosis. In addition, on histologic sections the metastatic tumor cells were found to express bcl-2 and CD44, markers that have been recently studied in cutaneous tumors. CONCLUSION: In acquiring metastatic potential, this lesion did not lose the molecular characteristics of bcl-2 and CD44 expression, the two features deemed to be important in the indolent behavior of BCC.

Microinvasive carcinoma (T1mic) of the breast: clinicopathologic profile of 21 cases.

Clinicopathologic data on microinvasive carcinoma of the breast (MICB) as defined by the 1997 TNM criteria (T1mic < or = 1 mm) is scarce. Histologic slides of 109 cases from 1993 through 1997, in which microinvasion was either suspected or diagnosed initially, were reviewed. A double immunoenzyme-labeling technique using antismooth muscle actin and anticytokeratin antibody on the same section was used to confirm invasion in equivocal cases. All foci of invasion were measured by ocular micrometer. Twenty-one cases were confirmed to be MICB. The mean age of the patients was 60.9 years. Thirteen patients presented with mammographic abnormalities on routine examination (60.9%). MICB was ductal in 18 patients, including one tubular carcinoma, and was lobular in three patients. The mean number of invasive foci was two per patient (range, one to seven foci). The accompanying duct carcinoma in situ had high-grade nuclei and necrosis in 16 of 18 patients (89%), 13 of which (72%) were comedo-type. Two of the 15 patients had one positive axillary lymph node each (13.3%). Eleven patients underwent mastectomy, nine received radiation therapy, one received chemotherapy, and two underwent lumpectomy only. Median follow up was 28 months (range. 18-63 months). One patient had a chest wall recurrence of infiltrating duct carcinoma and another recurred with duct carcinoma in situ.

Double immunolabeling with cytokeratin and smooth-muscle actin in confirming early invasive carcinoma of breast.

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this technique a useful diagnostic tool in the evaluation of those cases of breast carcinoma that exhibit equivocal invasion.

Prognostic significance of plasma prolactin in breast cancer: comparison with the expression of c erb B-2 oncoprotein.

Having established prolactin to be an indicator of disease progression and hyperprolactinemia as an independent predictor of short term prognostication, we have in this report compared plasma prolactin with the expression of c erb B-2 oncoprotein, ER and PR. c erb B-2 oncoprotein, ER and PR are determinants of breast cancer biology. This is a retrospective study of 47 breast cancer patients. When patients were grouped according to the stage of the disease, plasma prolactin was higher in patients with advanced disease than those with stage II disease. The patients were sub-grouped according to prolactin < 20.0 ng/ml and > 20.0 ng/ml. The expression of c erb B-2, ER and PR did not differ in these two sub-groups. The overall survival differed significantly between the two sub-groups of prolactin. The patients were sub-grouped according to c erb B-2 positivity or negativity, there was no significant difference in survival. c erb B-2 expression did not differ between the three grades of the tumor, nodal and receptor positivity or negativity. Hence, the present study reinforces the positive association between hyperprolactinemia and unfavourable prognosis and finds c erb B-2 expression as a weak prognosticator in advanced breast cancer patients.

Comparison of plasma prolactin and CEA in monitoring patients with adenocarcinoma of colon and rectum.

Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma.

Endocrine function in premenopausal and postmenopausal advanced breast cancer patients treated with CMF or tamoxifen.

The effect of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or tamoxifen treatment on endocrine function was investigated in premenopausal and postmenopausal breast cancer patients. CMF therapy resulted in ovarian failure but pituitary and adrenal functions were unaffected in premenopausal patients. Although amenorrhea was achieved within two to five months in older patients, younger patients required large cumulative doses of cytotoxic drugs to exhibit ovarian dysfunction. CMF therapy had no effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system. On the other hand, tamoxifen therapy in postmenopausal patients resulted in hyperestrogenemia.

Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast cancer patients.

Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and 15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH, prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and SHBG of Stage II breast cancer patients were compared with advanced patients and also with controls. In premenopausal patients the levels of steroid hormones were significantly low whereas those of peptide hormones were significantly high. On the contrary, in postmenopausal patients, except DHEA-S, all other hormones were significantly elevated in comparison with controls. In premenopausal patients, DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when compared with hormone levels of Stage II patients. In postmenopausal advanced breast cancer patients, when compared with Stage II patients, the levels of SHBG, LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione, estradiol, and progesterone decreased as stage advanced.

Central acinic cell carcinoma of the mandible: report of a case.

A case is reported of a central acinic cell carcinoma of the mandible. This is an unusual site for this rare tumour and to our knowledge only three cases have been previously reported in the literature.

Plasma prolactin as an indicator of disease progression in advanced breast cancer.

Serial plasma prolactin levels were measured in 144 breast cancer patients (premenopausal [PR-M], N = 64; postmenopausal [PO-M], N = 80) and compared with respective controls. Patients with breast cancer were grouped into those who (1) developed distant metastasis, (2) developed local recurrence, (3) stable disease, and (4) responded to the various therapeutic modalities at the end of 2 years. The authors' analysis showed excellent correlation between serial plasma prolactin changes and the response to therapy or progression of disease in patients with advanced breast carcinoma.

Oestrogen receptors in benign epithelial lesions and intraduct carcinomas of the breast: an immunohistological study.

We examined 198 breast lesions, representing commonly encountered benign epithelial proliferative disorders, lobular carcinoma in situ and intraduct carcinoma, immunohistologically for oestrogen receptors (ER). A mixture of three ER monoclonal antibodies--H222, D75 and D547--was used on sections of routinely processed and paraffin-embedded tissue blocks. Over 65% of the benign and malignant lesions showed some evidence of ER expression and significant staining was recorded by two observers in 28-31% of fibroadenomas, 18-28% of ductal epithelial hyperplasias, 30-40% of sclerosing adenosis cases, 38-45% of papillomas, 60% of in situ lobular carcinomas and 42-45% of intraduct carcinomas. Apocrine metaplastic cells and myoepithelial cells showed absent or only weak staining. Amongst intraduct carcinomas, less than 20% of comedo carcinomas and over 50% of cribriform, papillary and solid variants showed significant ER staining.

Pseudomembranous trigonitis of the bladder: hormonal aetiology.

Fourteen formalin fixed and paraffin wax embedded biopsy specimens from 10 women (age range 34-68) presenting with pseudomembranous trigonitis were studied using a combination of anti-oestrogen receptor monoclonal antibodies in an avidin-biotin immunoperoxidase technique. All epithelial areas showing vaginal metaplasia exhibited staining confined to the nucleus in the basal and parabasal layers of the squamous epithelium while no staining was encountered in adjacent trigonal transitional epithelium included in nine of the biopsy specimens. The selective expression of nuclear oestrogen receptor in trigonal epithelium affected by vaginal metaplasia in a distribution similar to that reported in vaginal epithelium by other workers lends further support to oestrogen mediated aetiology in this condition and is consistent with an embryological derivation of the trigone, distinct from that of the rest of the bladder.

Silver-binding nucleolar organizer regions (AgNORs) in benign and malignant breast lesions: correlations with ploidy and growth phase by DNA flow cytometry.

Silver-binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin-embedded tissue blocks and have been shown to assist in the distinction between benign and malignant lesions. We have examined 214 benign and malignant breast lesions by this method. The AgNOR counts were fibroadenomas 1.87 +/- 0.20 (mean +/- SD; n = 39), papillomas 1.92 +/- 0.21 (n = 28), sclerosing adenosis 1.96 +/- 0.24 (n = 23), epitheliosis 2.21 +/- 0.30 (n = 38), lobular carcinoma in situ 2.67 +/- 0.54 (n = 9), intraduct carcinoma 3.75 +/- 1.33 (n = 37), and invasive carcinoma 4.22 +/- 1.18 (n = 40). However, the counts in 25-30 per cent of epitheliosis lesions and intraduct carcinomas overlapped in the region of 2-3 AgNOR dots per nuclear profile. The AgNOR counts in carcinomas were also compared with ploidy and growth phase fractions (S + G2 + M%) by flow cytometry. Thirty-three of the 46 cancers with counts over 3 AgNOR dots per nuclear profile contained aneuploid cells (greater than 10 per cent of the total), whereas 8 of the 12 with counts below 3 comprised diploid cells only (P less than 0.05). Similar trends were noted with regard to growth phase fractions which were 19.15 per cent +/- 12.31 and 13.98 per cent +/- 5.55, respectively, for the two groups (P greater than 0.10). We conclude that this method alone does not offer a reliable histological discriminant for malignancy in the breast. However, AgNOR counting may provide information on breast cancer prognosis supplementary to that obtained from DNA flow cytometric analyses.

Silver-binding nucleoli and nucleolar organizer regions in fine needle aspiration cytology of the breast.

Silver staining was used to demonstrate nucleoli and nucleolar organizer regions (NORs) in cytopreparations from breast fine needle aspiration (FNA) biopsies, with the resulting black dots being a combination of silver-binding nucleoli and dispersed NORs. Discrete black dots in 200 nuclei were manually counted in 25 silver-stained biopsies; the cytologic diagnoses were made on routine Papanicolaou-stained cytopreparations from the same aspirates. Although malignant breast lesions showed higher counts than did benign breast disease, an overlap of one malignant and three benign lesions occurred. Therefore, the method cannot be recommended for reliably discriminating between malignant and benign routine breast specimens obtained by FNA; it may have some value in assessing tumor behavior.