Current Issue : July - September Volume : 2015 Issue Number : 3 Articles : 8 Articles
A duck was received for necropsy with history of dullness, anorexia and distended abdomen. On postmortem examination, cystic and papillary growth are seen in the ovary. Histopathological examination revealed multi branched papillae in the cyst lumen. Based on gross and microscopic lesions, the case was diagnosed as cyst adenocarcinoma....
A tumour mass was surgically incised from the oral cavity of a labrador dog and submitted to the Department of Pathology, College of Veterinary Science, Tirupati for histopathological confirmation. Grossly, the tumour mass was solitary, pinkish white and measured 5-8 cm in diameter. The mass was firm and white to pink colour on cut surface. Cytological smears revealed spindle shaped cells with pleomorphic nucleus. Histologically, the tumour mass revealed interlacing fascicules of spindled shaped cells with oval to elongated nuclei vesicular chromatin with blunt ended. Prominent Nucleoli with numerous mitotic figures were also observed. Based on gross, cytology and histopathology the tumour was diagnosed as oral leiomayosarcoma....
Background: The mutation in KRAS exon 2 is a validated biomarker of resistance to anti-epidermal growth factor\nreceptor (EGFR) therapy in metastatic colorectal cancer (mCRC). Several reports have confirmed associations of\nother RAS mutations with resistance to anti-EGFR therapy. However, the impact of BRAF and PIK3CA mutations on\nthe efficacy of anti-EGFR therapy remains controversial. Little is known about the frequencies and clinicopathological\nfeatures of these mutations, as well as the therapeutic effects of anti-EGFR therapy in mCRC patients with these\nmutations, especially in the Asian population.\nMethods: In this retrospective observational study, frequencies and clinicopathological features of KRAS, NRAS,\nBRAF and PIK3CA mutations were evaluated in patients with mCRC. Among patients treated with anti-EGFR therapy,\nobjective response, progression-free survival (PFS), and overall survival (OS) were evaluated according to gene status.\nResults: Among 264 patients, mutations in KRAS exon 2, KRAS exons 3 or 4, NRAS, BRAF and PIK3CA were detected in\n34.1%, 3.8%, 4.2%, 5.4% and 6.4%, respectively. Thus, a total of 12.1% of patients without KRAS exon 2 mutations had\nother RAS mutations. Primary rectal tumors tended to be more frequently observed in RAS mutant tumors. BRAF\nmutations were more frequently observed with right-sided colon, poorly differentiated or mucinous adenocarcinoma,\nand peritoneal metastasis. Among the 66 patients with KRAS exon 2 wild-type tumors treated with anti-EGFR agents,\nPFS (5.8 vs. 2.2 months) and OS (17.7 vs. 5.2 months) were significantly better in patients with all wild-type tumors (n = 56)\nthan in those with any of the mutations (n = 10). The response rate also tended to be better with all wild-type tumors\n(26.8 vs. 0%).\nConclusion: Other RAS and BRAF mutations were observed in KRAS exon 2 wild-type tumors, which were associated with\nsome clinicopathological features and resistance to anti-EGFR therapy in our patient cohort....
Background: Cyclin D1 and its kinase partners control cell cycle progression. Cyclin D1 is frequently deregulated in\nvarious cancers, including malignant hemopathies, and tumor cells display uncontrolled cell proliferation. Cyclin D1\nis not expressed in the B-cell lineage but is found in multiple myeloma (MM) cells in almost 50% of patients with\nthis condition. Paradoxically, cyclin D1 expression is associated with a good prognosis and longer overall survival in\nMM patients.\nMethods: We used two independent MM cell lines (RPMI 8226 and LP1) to generate several clones stably expressing\neither the green fluorescent protein (GFP) or a GFP-cyclin D1 fusion protein, and we analyzed the properties acquired\nfollowing cyclin D1 expression.\nResults: Whole-genome expression analysis in the cell clones indicated that cyclin D1 profoundly modified several\ncellular functions, including the regulation of apoptotic cell death. We studied the apoptotic response of GFP- and\nGFP-cyclin D1-expressing clones to bortezomib-treatment. We found that the apoptotic response occurred faster\nand was of a greater amplitude in cyclin D1-expressing cells. Cyclin D1 expression enhanced the caspase-dependent\napoptosis mediated by the intrinsic mitochondrial pathway. More importantly, cyclin D1 also activated the unfolded\nprotein response (UPR) and induced endoplasmic reticulum (ER) stress-mediated apoptosis.\nConclusion: The ER is well known to be a crucial regulator of plasma cell death and it plays the same role in their\nmalignant counterparts, myeloma cells. This role involves activation of the UPR controlled at least in part by cyclin D1...
Background: Gangliocytic paraganglioma (GP) is an extremely rare benign tumor that commonly arises from the\nsecond part of the duodenum. Since GP exhibit neither prominent mitotic activity nor Ki-67 immunoreactivity, this\ntumor is often misdiagnosed as neuroendocrine tumor (NET) G1 (carcinoid tumor). However, patients with GP may\nhave a better prognosis than patients with NET G1. This fact emphasizes the importance of differentiating GP from NET\nG1, but few studies have reported the epidemiology and histopathology of GP because of its rarity. To differentiate GP\nfrom NET G1 with ease, we conducted a multi-institutional retrospective study analyzing the morphometric and\nimmunohistochemical features of this tumor.\nMethods: Since only a limited number of patients with GP could be identified in our institute, we conducted a\nmulti-institutional retrospective study of GP in Japan, which was approved by the Ethics Committee of our medical\ninstitute. The obtained tissue sections underwent detailed morphometric and immunohistochemical analyses.\nAdditionally, to differentiate GP from NET G1 with ease, immunohistochemical findings were compared.\nResults: In our examination of 12 cases of duodenal GP, we found that epithelioid cells of GP exhibited positive\nreactivity for progesterone receptor and pancreatic polypeptide, whereas tumor cells of NET G1 were completely\nnegative reactivity for both. Additionally, although GP is considered to be an extremely rare NET, we found that\nfour (40.0%) of the ten patients at our institute with duodenal NET G1 actually had GP.\nConclusions: Although GP is regarded as a rare NET, our results suggest that it accounts for a substantial\npercentage of duodenal NETs. Additionally, confirmation of immunoreactivity for progesterone receptor and\npancreatic polypeptide can assist in differentiating GP from NET G1....
Background: NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein that catalyzes two-electron reduction and\ndetoxification of quinones and its derivatives. NQO1 catalyzes reactions that have a protective effect against redox\ncycling, oxidative stress and neoplasia. High expression of NQO1 is associated with many solid tumors including\nthose affecting the colon, breast and pancreas; however, its role in the progression of ovarian carcinoma is largely\nundefined. This study aimed to investigate the clinicopathological significance of high NQO1 expression in serous\novarian carcinoma.\nMethods: NQO1 protein expression was assessed using immunohistochemical (IHC) staining in 160 patients with\nserous ovarian carcinoma, 62 patients with ovarian borderline tumors and 53 patients with benign ovarian tumors.\nQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NQO1 mRNA expression levels.\nThe correlation between high NQO1 expression and clinicopathological features of ovarian carcinoma was evaluated\nby Chi-square and Fisher�s exact test. Overall survival (OS) rates of all of ovarian carcinoma patients were calculated\nusing the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional\nhazards regression model.\nResults: NQO1 protein expression in ovarian carcinoma cells was predominantly cytoplasmic. Strong, positive expression\nof NQO1 protein was observed in 63.8% (102/160) of ovarian carcinomas, which was significantly higher than in\nborderline serous tumors (32.3%, 20/62) or benign serous tumors (11.3%, 6/53). Importantly, the rate of strong,\npositive NQO1 expression in borderline serous tumors was also higher than in benign serous tumors. High expression\nof NQO1 protein was closely associated with higher histological grade, advanced clinical stage and lower OS rates in\novarian carcinomas. Moreover, multivariate analysis indicated that NQO1 was a significant independent prognostic\nfactor, in addition to clinical stage, in patients with ovarian carcinoma.\nConclusions: NQO1 is frequently upregulated in ovarian carcinoma. High expressin of NQO1 protein may be an effective\nbiomarker for poor prognostic evaluation of patients with serous ovarian carcinomas....
Background: Mammographic breast density and parenchymal patterns are well-established risk factors for breast\ncancer. We aimed to report inter-observer agreement on three different subjective ways of assessing mammographic\ndensity and parenchymal pattern, and secondarily to examine what potential impact reproducibility has on relative risk\nestimates of breast cancer.\nMethods: This retrospective caseââ?¬â??control study included 122 cases and 262 age- and time matched controls (765\nbreasts) based on a 2007 screening cohort of 14,736 women with negative screening mammograms from Bispebjerg\nHospital, Copenhagen. Digitised randomized film-based mammograms were classified independently by two readers\naccording to two radiological visual classifications (BI-RADS and TabÃ?¡r) and a computerized interactive threshold\ntechnique measuring area-based percent mammographic density (denoted PMD). Kappa statistics, Intraclass\nCorrelation Coefficient (ICC) (equivalent to weighted kappa), Pearsonââ?¬â?¢s linear correlation coefficient and limits-ofagreement\nanalysis were used to evaluate inter-observer agreement. High/low-risk agreement was also determined by\ndefining the following categories as high-risk: BI-RADSââ?¬â?¢s D3 and D4, TabÃ?¡rââ?¬â?¢s PIV and PV and the upper two quartiles\n(within density range) of PMD. The relative risk of breast cancer was estimated using logistic regression to calculate\nodds ratios (ORs) adjusted for age, which were compared between the two readers.\nResults: Substantial inter-observer agreement was seen for BI-RADS and TabÃ?¡r (?=0.68 and 0.64) and agreement was\nalmost perfect when ICC was calculated for the ordinal BI-RADS scale (ICC=0.88) and the continuous PMD measure\n(ICC=0.93). The two readers judged 5% (PMD), 10% (TabÃ?¡r) and 13% (BI-RADS) of the women to different high/low-risk\ncategories, respectively. Inter-reader variability showed different impact on the relative risk of breast cancer estimated\nby the two readers on a multiple-category scale, however, not on a high/low-risk scale. TabÃ?¡rââ?¬â?¢s pattern IV demonstrated\nthe highest ORs of all density patterns investigated.\nConclusions: Our study shows the TabÃ?¡r classification has comparable inter-observer reproducibility with well tested\ndensity methods, and confirms the association between TabÃ?¡rââ?¬â?¢s PIV and breast cancer. In spite of comparable high\ninter-observer agreement for all three methods, impact on ORs for breast cancer seems to differ according to the\ndensity scale used. Automated computerized techniques are needed to fully overcome the impact of subjectivity...
Background: AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon\ncancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in\nhuman endometrial cancer.\nMethods: Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional\nculture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell\nproliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by\nAF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were\ndetermined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from\nall patients before the study.\nResults: The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin\nshowed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA\ncellsââ?¬â?both weakly expressing AF-6/afadinââ?¬â?showed irregular gland-like structures and disorganized colonies with\nno gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in\n3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly\nAF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656)\nsuppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance\nto doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed\nthat AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade.\nConclusions: AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through\nthe ERK and Src pathway. The inhibitors to these pathways might be molecular-targeted drugs which suppress\nmyometrial invasion in endometrial cancer. AF-6/afadin could be a useful selection marker for fertility-sparing\ntherapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial\ninvasion. AF-6/afadin knockdown induced chemoresistance especially to cisplatin. Therefore, loss of AF-6/afadin\nmight be a predictive marker of chemoresistance to cisplatin....
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