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Aims: To clarify which immunohistochemical markers could be helpful in distinguishing between classical Hodgkin's lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBCL) to more narrowly define 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and cHL'., Methods and Results: Two hundred and 83 cHLs and 51 PMBCLs were analysed on validated tissue microarray platforms with antibodies to BOB.1, CD15, CD20, CD23, CD30, CD79a, cyclin E, LMP-1, MUM1p, p63 and Oct2. The marker cut-off scores were calculated using receiver-operating characteristic curves. Markers with the highest positive predictive value for cHL were: CD15, cyclin E, LMP-1 (all 100%), MUM1p (93%) and CD30 (83%). High sensitivity was achieved only by CD30 (92%) and cyclin E (79%). Nineteen percent of PMBCLs were also positive for CD30, which led to a lower specificity of CD30 as regards cHL (81%) compared with cyclin E (100%). The antibodies with the highest positive predictive value for PMBCL were: CD23 (98%), p63 (96%), BOB.1 (94%) and CD79a (90%), with high sensitivity for BOB.1 (100%), CD79a (89%) and p63 (82%)., Conclusions: The use of at least three of the most accurate immunohistochemical markers, cyclin E, CD79a and BOB.1, may be helpful in the differential diagnosis of cHL and PMBCL.

Aims: To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis., Methods and Results: Using a high-throughput tissue microarray technique, 169 specimens from gastric carcinomas, precursor lesions and normal mucosa were immunostained on a series of tissue chips for p53, p21(WAF1/CIP1) cyclin E, Bcl-2, c-met and mucin 5AC expression. The overexpression of p53 was observed in 10.7% of low-grade dysplasia (LGD), 38.1% of high-grade dysplasia (HGD) and 39.6% of intestinal type gastric carcinoma (IGC). Expression of p21(WAF1/CIP1) was found in 47.6% of incomplete intestinal metaplasia (IM), 36.7% of dysplasia (Dys) and 29.5% of IGC. The overexpression of cyclin E was more frequently present in carcinomas than in Dys (P < 0.05); moreover, high-level expression (> 25% in extent) of cyclin E was observed only among IGC. Abnormal Bcl-2 expression was present in 81.0% of incomplete IM, 69.4% of Dys and 22.9% of IGC. Along with progression of the lesion, the expression of c-met increased; in contrast, mucin 5AC decreased gradually., Conclusions: The specific expression pattern in incomplete IM was mucin 5AC+/Bcl-2+/p53-/cyclin E-, while mucin 5AC-/cyclin E+ was specific for IGC. p53 was useful for distinguishing LGD from HGD. High-level expression of cyclin E might be an indicator for malignant transformation of dysplasia.

Aims: Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive variant of fibrosarcoma and has been reported to have metastatic potential despite its low-grade histological findings. Low-grade myxofibrosarcoma (MFS) is an important differential diagnosis of LGMFS, because it shows different biological behaviour. Of 75 MFSs in the extremities and trunk, we defined 22 grade 1 tumours as low-grade MFS according to the French Federation of Cancer Centres grading system and compared the clinicopathological factors and immunohistochemical expression of cell cycle regulators with those of 11 LGFMSs., Methods and Results: The two entities could be distinguished on histological grounds. Low-grade MFS was characterized by the presence of prominent elongated, curvilinear capillaries and pseudolipoblasts, accompanied by an abundant myxoid matrix. It had no extensive solid areas. LGFMS was composed of bland spindle cells arranged in a whorled pattern with alternating myxoid and fibrous stroma. Curvilinear capillaries were not prominent and cytological atypia was absent. No tumour necrosis was observed in any of the 11 LGFMSs, whereas only one case showed tumour necrosis in less than 50% of the tumour in 22 low-grade MFSs. The patients with low-grade MFS were significantly older than those with LGFMS (low-grade MFS average, 60.1 years; LGFMS average, 31.5 years; P < 0.0001) and low-grade MFS occurred more frequently in a superficial location (low-grade MFS 14/20; LGFMS 2/11; P = 0.0077). As for cell cycle regulator expression, the MIB-1 labelling index (LI) (14.76 on average) and cyclin E LI (11.55 on average) in low-grade MFS were significantly higher than those (MIB-1 LI, 4.68 on average; cyclin E LI, 3.38 on average) of LGFMS, while p21 LI (25.53 on average) and p27 LI (42.68 on average) in low-grade MFS were significantly lower than those (p21 LI, 42.74 on average; p27 LI, 57.28 on average) of LGFMS., Conclusions: We conclude that low-grade MFS and LGFMS are distinctly different clinicopathological entities and the assessment of the immunohistochemical expression of MIB-1, cyclin E, p21 and p27 as well as conventional clinicopathological features may be helpful to distinguish low-grade MFS from LGFMS.

Aims: Cell cycle regulatory proteins were analysed by immunohistochemistry in order to clarify how their expression changes with the degree of atypia as oesophageal surface squamous epithelium progresses from normal mucosa, through reactive change, low-grade dysplasia, and high-grade dysplasia to mucosal invasive carcinoma., Methods and Results: Immunostaining for cyclin D1, cyclin E, p21, p27, p53 and Ki67 proteins was performed using 22 normal mucosa, 17 reactive change, 22 low-grade dysplasia, 15 high-grade dysplasia and 22 mucosal invasive carcinoma specimens. Normal mucosa, low-grade dysplasia and high-grade dysplasia samples were taken from patients without any oesophageal invasive carcinoma by endoscopic biopsy or endoscopic mucosal resection, and reactive change and mucosal invasive carcinoma were obtained from oesophagectomy material. Stepwise over-expression of cyclin E (P < 0.0001) and p53 (P < 0.0001), reduction of p21 (P=0.0189) and dysregulation of cyclin D1 and p27 were observed in the multistep process of oesophageal carcinogenesis. Significant differences in expression of p27 (P < 0.0001), p53 (P=0.0299) and Ki67 (P=0.0101) were observed between reactive change and low-grade dysplasia. Furthermore, expression of cyclin D1, cyclin E, p27 and p53 in mucosal invasive carcinoma were significantly different from those in high-grade dysplasia (P=0.0079, P=0.0237, P=0.0042 and P= 0.0299, respectively)., Conclusions: Cell cycle regulatory proteins, cyclin E, p53 and p21 show stepwise over-expression or reduction with progression of oesophageal carcinogenesis, correlating with the increased cell proliferation observed with Ki67 labelling. We conclude that immunohistochemical analysis for p27, p53 and Ki67 is practically useful for the discrimination between low-grade dysplasia and reactive change. Cyclin D1, cyclin E, p27 and p53 help to distinguish high-grade dysplasia from mucosal invasive carcinoma.