Gleason scores from biopsy and RP specimens. Concordance was evaluated using the κ coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses. RESULTSThe Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy-based Gleason score more often under-graded (38%) than overgraded (9%) the RP-based Gleason score. Pathology units that examined > 40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lowervolume units. The rate of upgrading from a Gleason score of ≤ 6 in the biopsy to ≥ 7 in the RP specimen increased with increasing preoperative prostate-specific antigen serum levels, and with increasing intervals between biopsy and RP. CONCLUSIONSThe concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.

BackgroundThis study describes time-trends on epidemiology, subtypes and histopathological entities of osteosarcoma (OS) in a nationwide and unselected cohort of OS patients in Norway between 1975 and 2009. Few nationwide studies are published, and we still have particularly limited knowledge regarding patients not included in clinical trials comprising about half of the OS population.MethodHistologically verified skeletal OS for all subgroups were included, resulting in 473 eligible cases from a total of 702 evaluated patients. To ensure completeness, the present cohort was based on all cases reported to the Norwegian Cancer Registry, complemented with data from all Norwegian hospitals involved in sarcoma management. Survival analyses were performed with overall and sarcoma-specific survival as endpoints.ResultsMean annual age-standard incidence amounted to about 3.8 per million in male and 2.8 per million in female with no clear time-trends. The male to female ratio was 1.4. Peak incidence was observed in the second decade for both genders. Conventional OS comprised 71.2% of all cases, while low grade OS represented 10.4% and telangiectatic OS only 1.3%. The most common primary site of OS was femur and tibia, respectively. The axial to appendicular ratio increased with the age. The overall 10-year survival did increase from about 30% during the late 1970s to around 50% 20 years later, with no subsequent improvement during the last two decades. Axial tumours, age above 40 years and overt metastatic disease at time of diagnosis were all negative prognostic factors.ConclusionNo improvement in the overall survival for OS since the 1990s was documented. The survival rates are still poor for elderly people, patients with axial disease and in the primary metastatic setting. The average incidence rate of skeletal OS in Norway was in line with international figures.

Background  Methyl 5‐aminolaevulinate (mALA) is an ester derivative of 5‐aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA. Objectives  To assess long‐term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA‐based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment. Methods  Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2–4 years (mean 35 months) after mALA‐PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g−1 was applied to all tumours for 24 h or 3 h before illumination from a broad‐band halogen light source with light doses from 50 to 200 J cm−2. Fibrosis was assessed histologically in 23 biopsies. Results  The overall cure rate for 350 BCCs, including non‐responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies. Conclusions  We conclude that mALA‐based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.

BACKGROUND: Recent work has suggested a role for nuclear factor jB (NF-jB) in the propagation of ovarian cancer cell lines, but the significance and mechanism of NF-jB in ovarian cancer is unknown. The authors hypothesized that the NF-jB pathway is over activated in aggressive ovarian cancers. METHODS: The levels of 3 NF-jB transcription factors, the activating inhibitors of NF-jB (IjB) kinases, and the NF-jB target matrix metalloproteinase 9 (MMP9) were assessed by immunohistochemistry in specimens of ovarian cancer that were obtained at diagnosis from a cohort of 33 patients who subsequently received combined paclitaxel, cisplatin, and cyclophosphamide. Associations were made between NF-jB pathway proteins and outcome. The validation of coexpression was performed at the gene level in 2 independently collected cohorts of 185 and 153 ovarian cancers. RESULTS: The presence of NF-jB proteins in newly diagnosed advanced ovarian cancers was established, and a potential association with overall survival was identified. Transcription factors p65 and v-rel reticuloendotheliosis viral oncogene homolog B (RelB) were coexpressed with IjB kinase a, 1 component of a key trimolecular regulatory complex. Coexpression of the NF-jB machinery suggested activity of NF-jB signaling in these ovarian tumors. A significant association of p50 with poor overall survival was observed (P ¼ .02). MMP9 expression had the opposite association, in which patients who had tumors without MMP9 staining had the poorest prognosis (P ¼ .01), and this association held true at the gene expression level in an independently collected cohort of 185 ovarian cancers. CONCLUSIONS: The deregulation of NF-jB activity may influence outcome in women who receive standard therapy for advanced ovarian cancer. Modification of the NF-jB pathway may present an opportunity to improve outcome in the subset of women who have pathway activity. Cancer 2010;116:3276-84.

The detection of malignant cells in pleural, peritoneal, and pericardial fluids of cancer patients marks the presence of metastatic disease and is associated with a grave prognosis. We evaluated five epithelial markers for the detection of cancer cells in 94 fresh pleural, peritoneal and pericardial effusions. Eighty-four of the samples were regarded as adequate for analysis after evaluation of cytological smears, including 61 samples from patients known to have gynaecological neoplasms. The other 23 samples were from patients with various non-gynaecological malignancies or tumours of unknown origin. Our control cases were 10 fallopian tubes not affected by any malignancy and 12 malignant mesotheliomas. Cell blocks from all cases were stained for CA-125, BerEP4, carcinoembryonic antigen (CEA), BG8 (Lewis Y blood antigen), and B72.3 (TAG-72). Fifty-one of 84 cases were diagnosed as malignant or suggestive of malignancy in cytological smears and/or cell block sections. However, staining for epithelial markers highlighted the presence of malignant cells in 7 additional cases. When membrane staining was evaluated, the sensitivity of the markers studied in detecting malignant cells was as follows: CA-125: 88%, BerEP4: 78%, CEA: 26%, BG8: 86%, B72.3: 79%. Membrane positivity for CEA, B72.3 and BerEP4 was not detected in reactive mesothelial cells. However, membranous staining in mesothelial cells was evident in 13% and 31% of cases with the use of BG8 and CA-125, respectively. Weak cytoplasmic staining for CEA was observed in mesothelial cells in 2 cases. When Ber-EP4, B72.3, and BG8 staining results in cancer cells were combined, the following sensitivity levels were observed: BG8+B72.3: 91%; BG8+Ber-EP4: 90%; B72.3+Ber-EP4: 93%; BG8+Ber-EP4+B72.3: 95%. The detection of malignant cells in effusions is facilitated by the use of immunocytochemistry using a wide panel of antibodies. BerEP4 and B72.3 appear to be the best markers when both sensitivity and specificity are considered, followed by BG8, while CEA and CA-125 have a limited role in the detection of metastases from gynaecological tumours owing to the low sensitivity of the former and the low specificity of the latter. Analysis of all staining results should be based on a thorough morphological examination.

US-guided PEI treatment of metastatic lymph nodes seems to be an excellent alternative to surgery in patients with a limited number of neck metastases from PTC. This procedure should replace "berry picking" surgery.

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Purpose: The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of proteases, laminin receptors (LRs), and transcription factors involved in invasion and metastasis.Experimental Design: The material studied consisted of 60 malignant pleural effusions from breast cancer patients and 68 corresponding solid tumors (37 primary and 31 metastatic tumors). Expression of matrix metalloproteinases [MMPs (MMP-1, MMP-2, MMP-9, and MMP-14)], the MMP inhibitor tissue inhibitor of metalloproteinase-2, the MMP inducer EMMPRIN, the 67-kDa LR, the ␣ 6 integrin subunit, and the transcription factors AP-2, Ets-1, and PEA3 was studied using immunohistochemistry, mRNA in situ hybridization, reverse transcription-polymerase chain reaction, zymography, and flow cytometry. Hormone receptor (estrogen receptor and progesterone receptor) status and c-erbB-2 status were also studied.Results: Significantly reduced estrogen receptor (P < 0.001) and progesterone receptor (P ‫؍‬ 0.001) expression was seen in effusions compared with primary tumors, with opposite findings for c-erbB-2 (P ‫؍‬ 0.003). Tumor cell MMP-2 protein expression in effusions was higher than that in primary tumors (P < 0.001) and lymph node metastases (P ‫؍‬ 0.01). In situ hybridization demonstrated higher MMP-2 (P ‫؍‬ 0.007), PEA3 (P ‫؍‬ 0.038), and EMMPRIN (P ‫؍‬ 0.026) mRNA expression in effusions. The time to progression from primary tumor to effusion was significantly shorter for patients whose primary tumors expressed MMP-1 (P ‫؍‬ 0.016) and who expressed the 67-kDa LR protein in primary tumor (P ‫؍‬ 0.007) and effusion (P ‫؍‬ 0.015).Conclusions: Our data provide documented evidence of molecular events that occur during the progression of breast carcinoma from primary tumor to effusion. The coordinated up-regulation of MMP-2 and Ets transcription factors in carcinoma cells in effusions is in full agreement with our previous reports linking these factors to poor prognosis in ovarian cancer. The rapid progression to effusion in cases showing MMP-1 and 67-kDa LR expression in primary tumor cells links aggressive clinical behavior with expression of metastasis-associated molecules in this setting.