Tumor budding and dedifferentiation in gallbladder carcinoma: Potential for the prognostic factors in T2 lesions
Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Nabesima 5-1-1, Saga City, Saga, 849-8501, Japan.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (Impact Factor: 2.65). 07/2011; 459(4):449-56. DOI: 10.1007/s00428-011-1131-9
Dedifferentiation (DD) is often encountered in gallbladder carcinoma (GBC) and poor prognosis with budding (BD) has been reported for other malignancies. However, the features of DD and BD in GBC remain unclear. The purpose of this study was to clarify the features and prognostic potential of DD and BD in GBC. A total of 80 patients with GBC (excluding intramucosal cancer) were enrolled. DD was histopathologically evaluated as tumors in which the grade of the invasive front is higher than the grade at the surface. BD was defined as an isolated single cancer cell or a cluster of fewer than five cancer cells at the invasive front. Of the 80 patients, 47 (58.8%) were positive for BD and 33 (41.2%) were positive for DD. Both BD and DD correlated significantly with disease-specific survival in univariate analysis (P < 0.0001 and P = 0.0013, respectively), but they were not identified as independent prognostic factors by multivariate analysis. In univariate analysis according to T stage, both BD and DD correlated significantly with survival in patients with T2 (n = 32) tumor (P = 0.0011 and P = 0.0018, respectively), whereas no prognostic impact in patients with T1b (n = 8), T3 (n = 34), or T4 (n = 6) tumor. Both DD and BD are frequently observed in GBC and reflect prognosis, particularly for T2 lesions. Therefore, the status of BD and DD should be taken into consideration in pathological reports on GBC.
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ABSTRACT: Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P=0.0004), lymph node (LN) metastasis (P<0.0001), distant metastasis (P=0.008), and stage (P=0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P=0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P=0.0178) and LN metastasis (P=0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2011; 459(6):573-80. DOI:10.1007/s00428-011-1155-1 · 2.65 Impact Factor
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ABSTRACT: Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic management. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of adjuvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Well-designed multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase III trials may provide relevant information.World Journal of Gastroenterology 06/2012; 18(21):2591-6. DOI:10.3748/wjg.v18.i21.2591 · 2.37 Impact Factor
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ABSTRACT: We investigated the prognostic value of tumor budding in 160 cases of operable invasive ductal carcinoma, not otherwise specified (IDC-NOS). The number of buds was counted in H&E slides with a maximal invasive margin in a 0.950mm(2) field of vision (200×). According to a cut-off score selected by ROC analysis, the cohort was dichotomized into a low (0-7 budding foci, 107 cases, 66.9%) and a high-grade budding group (8 or more budding foci, 53 cases, 33.1%). The inter-observer test showed a good reproducibility with 0.717 as the К value. High-grade budding was significantly associated with the presence of lymphovascular invasion (LVI) (P=0.001), larger tumor size (P=0.014), and worse clinical outcome (P<0.001). By immunohistochemical staining, budded cells at the margin displayed epithelial mesenchymal transition (EMT)-like molecular phenotype and decreased proliferative activity. Survival analyses revealed that tumor budding (HR 4.275, P<0.001) together with tumor size (HR 2.468, P=0.002), node status (HR 2.362, P<0.001), and LVI status (HR 1.910, P=0.035) was the independent prognostic factor in IDC-NOS. In conclusion, tumor budding is a reproducible, significant, and independent histopathological prognostic factor in IDC-NOS.Pathology - Research and Practice 04/2013; 209(5). DOI:10.1016/j.prp.2013.01.009 · 1.40 Impact Factor
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