摘要:

The model of colorectal tumorigenesis put forward by Fearon and Vogelstein has had great influence on molecular oncology. They proposed that a series of mutations occur in the progression from normal cells to colorectal cancer and that these mutations are associated with the histological features of such tumours. Several postulates of the model appear to be correct, particularly its emphasis on the stepwise accumulation of genetic changes and the inclusion of mutations at the adenomatous polyposis coli (APC) andTP53loci. Since the publication of the original model, however, mutations at other loci have been identified which may be alternatives or additions. There is also evidence to suggest that some colorectal cancers develop along a different genetic pathway. In this review, we discuss how tumour development can occur as Darwinian evolution through selection of advantageous somatic mutations. The non‐random nature of mutation selection gives rise to genetic pathways of tumorigenesis. In addition, we consider the Fearon and Vogelstein model, its shortcomings and possible additions to it. The evidence suggests that not all colorectal cancers follow the same genetic pathway during carcinogenesi

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.339381.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The abnormal expression of blood group related antigens has been reported in many malignant tumours; however, such expression in cholangiocarcinoma has not been examined systematically. The expression of blood group‐related antigens (A, B, H, Lewisa, Lewisb, Lewisx, Lewisy, carbohydrate antigen 19‐9 and carcinoembryonic antigen) was investigated immunohistochemically in 75 cases of cholangiocarcinoma (31 peripheral type and 44 hilar type). In non‐neoplastic bile ducts, A, B, and H antigens were expressed in large bile ducts, while Lewisa,b,yand carbohydrate antigen 19‐9 were variably expressed in both large and small bile ducts. Lewisxand carcinoembryonic antigen was not found in non‐neoplastic bile ducts. In cholangiocarcinomas, A, B, and H, antigens were more frequent in the hilar type than in the peripheral type, although the difference was not significant. The expression of the blood‐group related antigens, particularly A, Lewisa,b,y, carcinoembryonic antigen, and carbohydrate antigen 19‐9, was frequent in the tumour cells in well differentiated adenocarcinomas, while their immunoreactivity was less frequent in poorly differentiated adenocarcinomas. The superanuclear and luminal expression of these antigens in carcinoma cells was frequent in well differentiated adenocarcinomas, and the diffuse, cell membranous and stromal expression of these antigens was relatively frequent in poorly differentiated adenocarcinomas and adenosquamous carcinoma. The A, B, and H immunoreactivity of both non‐neoplastic bile ducts and cholangiocarcinomas was consistent with the host blood group type. These findings suggest that both the expression and intracellular distribution of blood group‐related antigens in cholangiocarcinoma are related to the differentiation of cholangiocarcinoma and, possibly, to the

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.343384.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Stereotactic core biopsy was performed on 200 women for 206 mammographically suspicious non‐palpable lesions detected over a period of 2 years as part of the Australian national programme for early detection of breast cancer. This study aimed to assess the reliability of stereotactic core biopsy in this context and to develop a protocol for the evaluation of stereotactic core biopsy in mammographically detected non‐palpable breast lesions. Fifty‐one of 52 malignant lesions found by stereotactic core biopsy were confirmed by excision biopsy (one woman declined excision). Nine (4.5%) women had atypical ductal hyperplasia on stereotactic core biopsy; at excision, six were low grade carcinomas (in situ or invasive carcinomas), one was a 3 mm focus of grade 3 invasive duct carcinoma, one was atypical ductal hyperplasia, and one patient refused excision biopsy. In 29 (14.5%) women the histology of the stereotactic core biopsy was considered not to correlate with the radiological abnormality, and excision biopsy was advised: in four of these women carcinomas were found. One hundred and ten (55%) women had 116 benign lesions on stereotactic core biopsy: on follow‐up, one of these patients has been found to have a carcinoma. Core biopsy number and sequence were analysed demonstrating that no particular biopsy was more diagnostic than any other, and that the diagnostic yield of three cores was statistically equal to that of five cores. The procedure was well‐tolerated and there were few complications. Thus, stereotactic core biopsy is an accurate and safe method for diagnosis of mammographically detected non‐palpable breast lesions, and we believe it is the diagnostic technique of choice in breast cancer screening programmes. However, a stereotactic core biopsy diagnosis of atypical ductal hyperplasia requires excision biopsy since a diagnosis of low grade intraduct carcinoma cannot be excluded. Furthermore, if tissue obtained by stereotactic core biopsy does not correlate with the mammographic abnormality, excision biopsy should

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.332376.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The expression of the nm23‐H1gene has been suggested to have an inverse association with metastases in certain tumours. The aim of this study was to investigate the relationship of nm23‐H1immunohistochemical expression with pathological tumour variables and survival in a series of transitional cell carcinomas (TCCs) of the bladder. Formalin‐fixed, paraffin‐embedded archival tissue from 87 carcinomas (Ta‐T145 cases) and T2‐T4(42 cases) was immunostained (Strept ABC/ HRP) with the NDPK‐A monoclonal antibody (NDPK‐A) against nm23‐H1protein. The tumours had already been evaluated for immuno‐expression of p53 protein. In addition, DNA analysis was performed by flow cytometry. Results were analysed using the linear trend in proportions test, the Fisher’s exact test and multivariate analysis. Paradoxically, advanced tumour stage showed significant correlation with nm23‐H1immunopositivity in muscle invasive TCCs (Pt = 0.01). Patients with nm23‐H1positive, muscle invasive TCCs had a worse prognosis at a level of suggestive statistical significance (PF = 0.08). In multivariate analysis, using a Cox’s proportional hazards survival model with six variables, tumour grade, disease stage and synchronous p53 and nm23‐H1detection showed significant correlation with poor patient survival (P = 0

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.336375.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

We investigated the relationship between immunohistochemical estimates of proliferative activity and expression of bcl‐2 protein and mutant p53 protein in 23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of proliferative activity was analysed and correlations between the variables and with mitotic score were investigated. Proliferative activity was assessed by use of monoclonal antibody MIB‐1 and staining for iododeoxyuridine (IdUrd), and evaluated in multiple, random, systematically sampled fields of vision. MIB‐1 indices were higher than those of IdUrd but for each case the two values were positively correlated (r = 0.78). The MIB‐1 index correlated positively with mitotic score (2P < 0.001) and malignancy grade (2P = 0.001). The intra‐observer reproducibility of the MIB‐1 and IdUrd indices were excellent (r = 0.98 andr = 0.90, respectively). p53 expression was detected in 43% and strong bcl‐2 expression was present in 57% of the studied cases. Expression of p53 and bcl‐2 were not significantly correlated to proliferative activity or the histological features. We conclude, that the MIB‐1 index is a reliable and reproducible estimate of proliferative activity and might improve the accuracy of conventional malignancy grading of soft tissue sarcomas. Furthermore, the results indicate that neither mutant p53 protein nor bcl‐2 oncogene alone are sufficient to induce in

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.333377.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Many classification schemes have been proposed for ductal carcinoma in situ. Architectural heterogeneity is widely recognized. Cytonuclear grade appears to have greater prognostic significance than architectural pattern. This study assesses heterogeneity using a classification based on cytological grade and compares this to architectural heterogeneity in mammographically detected ductal carcinoma in situ. One hundred and twelve cases were classified according to architectural subtypes and the carcinoma nuclei were graded. Necrosis and micro‐ calcification were assessed. Eighty‐four percent of ductal carcinomas in situ had a single nuclear grade, whereas only 39% showed a single architectural pattern. High grade nuclei were present in 87% of cases. Necrosis was associated with high nuclear grade. In contrast to architectural heterogeneity, this study shows little ductal carcinoma in situ heterogeneity when classification is based on nuclear grade. Thus, a cytomorphological classification should have the advantage of consistency and reproducibility in comparison to architecture‐based classification sy

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.322365.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

A case of sclerosing epithelioid fibrosarcoma arising in the thigh of a 40‐year‐old man is reported. This recently described sarcoma has a distinctive histological appearance which may cause confusion with a variety of other sarcomas with an epithelioid pattern, and indeed with benign soft tissue tumours showing hyalinization. Despite its bland cytology, sclerosing epithelioid fibrosarcoma is capable of metastases, often several years after surgical removal. The patient described here developed lung metastases five years after excision and remains alive a further three years later. The differential diagnosis and possible histogenesis are discus

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.342383.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

A 33‐year‐old Japanese woman presented with a polypoid 2.5 × 2.5 × 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal‐type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal‐type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial‐myoepithelial combination in the glands as seen in so‐called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal‐type cells co‐expressed PKK1 and vimentin. Staining for S‐100 protein, muscle actin, alpha‐smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.331373.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.297345.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0309-0167    

DOI:10.1046/j.1365-2559.1996.t01-1-297345.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY