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Purpose: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatinbased induction chemotherapy. Experimental Design: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1immunohistochemical expression. Results: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1expression. ERCC1and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value. Conclusion: Our results suggest that those patients characterized by low ERCC1expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1expression.

S U M M A R Y p63 is essential for epithelial cell survival and may function as an oncogene. We examined by immunohistochemistry p63 expression in human normal and tumor salivary gland tissues. In normal salivary glands, p63 was expressed in the nuclei of myoepithelial and basal duct cells. Among 68 representative salivary gland tumors, 63 displayed p63 reactivity. In all tumor types differentiated towards luminal and myoepithelial lineages (pleomorphic adenomas, basal cell adenomas, adenoid cystic carcinomas, and epithelialmyoepithelial carcinomas), p63 was expressed in myoepithelial cells, whereas luminal cells were always negative. Similarly, in mucoepidermoid carcinomas, basal, intermediate, and squamous cells expressed p63, in contrast to luminal mucous cells. p63 reactivity was also restricted to basal cells in Warthin tumors and oncocytomas. Myoepitheliomas and myoepithelial carcinomas all expressed p63. The only five negative tumors were three of four acinar cell carcinomas and two of three adenocarcinomas. In conclusion, p63 is expressed in the nuclei of normal human salivary gland myoepithelial and basal duct cells. p63 expression is retained in the modified myoepithelial and basal cells of human salivary gland tumors, which suggests a role for p63 in oncogenesis of these complex tumors.

Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are consistently benign lesions. Clinically, adenomyoma mimics frequently ampullary adenoma or carcinoma, and biopsy analysis is often difficult. The histogenesis of ampullary adenomyoma and adenomyomatous hyperplasia is still subject to debate. We present a retrospective study of clinicopathological features of 13 cases of surgically resected ampullary adenomyoma. The age of our patients was between 38 and 78 years (mean: 63 y). The preoperative diagnosis was ampullary tumor or tumor of the head of the pancreas. On macroscopy, a white, firm lesion of the ampullary wall was observed; its size ranged between 10 and 30 mm. Histologically the lesion consisted of multiple glandular structures surrounded by a fibroblastic/ myofibroblastic proliferation, resulting in a "pseudo-hypertrophy" of the Vaterian system. The immunophenotype of the epithelial component was cytokeratin 7؉/cytokeratin 20؊, similar to that of the normal biliary and pancreatic duct system. The epithelial cells exhibited low proliferative activity. The hyperplastic myofibroblastic cells expressed smooth muscle actin. A complete pancreatic heterotopy contiguous with the adenomyoma was noted in three cases. Adenomyoma and adenomyomatous hyperplasia of the Vaterian system are benign lesions frequently treated by extensive surgery because of long-term biliary obstruction. The clinicopathological characteristics suggest either a reactive and/or a malformative, nonneoplastic nature for this lesion, which could, in some cases, develop from heterotopic pancreas. The immunophenotype of epithelial cells may be a useful tool for differentiating it from ampullary adenoma on biopsy specimens.

Purpose:Tumour epithelial vimentin expression is a marker of mesenchymal differentiation and may be a useful marker of carcinomas with more aggressive behaviour. The aim of this study was to determine the extent and prognostic significance of vimentin expression in pancreatic ductal adenocarcinomas.Methods:Vimentin expression was detected by immunohistochemistry on tissue microarrays of surgically resected pancreatic ductal adenocarcinomas from 387 patients. The percentage of vimentin-immunolabelled neoplastic cells was correlated with outcome and with clinico–pathological factors using the Kaplan–Meier method and Cox multivariate survival models.Results:In all, 45% of primary pancreatic adenocarcinomas contained neoplastic cells that expressed vimentin, and in 27.5% of the cancers >10% of cells expressed vimentin. Vimentin expression was correlated with poor histological differentiation. By both uni- and multivariate survival analysis, neoplastic vimentin expression (P<0.01, HR 1.52, 95% confidence interval 1.14–2.04) was an indicator of a shorter postsurgical survival independent of other clinico–pathological variables.Conclusion:The presence of vimentin-expressing tumour epithelial cells in surgically resected pancreatic adenocarcinomas independently predicted a shorter postsurgical survival.

Although vascular invasion is a well-established indicator of poor prognosis for patients with infiltrating ductal adenocarcinoma of the pancreas (PDAC), the histopathologic characteristics of vascular invasion are not well described. Hematoxylin and eosin stained slides from 209 surgically resected infiltrating PDACs were systematically evaluated for the presence or absence of microscopic vascular invasion. For the cases with vascular invasion, we further categorized the histologic pattern of invasion into conventional and pancreatic intraepithelial neoplasia-like (PanIN-like). In addition, several histopathologic factors in the surrounding blood vessels, including lymphocytic infiltration and luminal fibrosis were carefully accessed. Data were compared to clinicopathologic variables, including patient survival. Microscopic vascular invasion was observed in 136 of the 209 PDACs (65.1%). Vascular invasion mimicking pancreatic intraepithelial neoplasia (PanIN-like invasion) was observed in 94 of the 136 cases (69.1%) with vascular invasion. Microscopic vascular invasion was associated with increased tumor size (p=0.04), higher pT classification (p=0.003), lymph node metastasis (p<0.0001), and perineural invasion (p=0.005). Vascular invasion was inversely correlated with neo-adjuvant therapy (p<0.0001). Examination of adjacent blood vessel revealed that peritumoral blood vessels with intimal lymphocytes (p=0.002), intimal (p=0.007) and medial (p=0.001) fibrosis, and cancer cells in vascular wall (p<0.0001), were all highly associated with intraluminal vascular invasion. In univariate analysis, patients whose cancers had microscopic vascular invasion (median survival, 12.9 months) had a significantly worse survival than did patients with carcinomas without vascular invasion (17.6 months; p=0.01, log-rank test). Microscopic vascular invasion is a poor prognostic indicator and can histologically mimic PanIN.

There are three patterns of MR imaging features of liver adenomatosis that are associated with three pathologic forms (steatotic, peliotic, and mixed).

Juvenile polyposis syndrome is a hamartomatous intestinal polyposis associated with malignant changes in 20% of patients at an early age. Germline mutations mostly involve two genes, SMAD4 and BMPR1, with no strong evidence of phenotype-genotype correlation, which could be predictive of the specific long-term evolution. In contrast, PTEN mutations are more commonly associated with Cowden and related diseases. Forty-two unrelated patients affected by juvenile polyposis syndrome were analyzed for germline alterations in the BMPR1A and SMAD4 genes, and for clinical and histological features. Deleterious mutations were found in 14/42 (33%) patients: 5 in BMPR1A and 9 in SMAD4. Low-grade adenomas were present in both SMAD4 and BMPR1A mutation carriers; only patients with SMAD4 mutations harbored carcinoma lesions (5/9). Malformative vessels were present in all SMAD4 related polyps when the mutation involved codons prior to position 423. No gastric polyps were observed in BMPR1A mutation carriers. SMAD4 germline mutations are responsible for a more aggressive digestive phenotype in patients with juvenile polyposis. The presence of malformative vessels within the stromal component might be a useful tool to drive the subsequent genetic and clinical management.