c-erbB-2 expression in benign and malignant breast disease.

An antibody, 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (approximately 14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis

Ungentlemanly Capitalism: John Hay and Malaya, 1904-1964

John Hay was one of Britain’s leading colonial capitalists, building his career from the 1900s to the 1960s in Malaya’s plantation industry. He became the leading spokesperson for the British rubber growers, and played a major role in the formulation of international restriction schemes during the 1930s. Hay was a remarkable entrepreneurial talent, consolidating his corporate power through the premiere Malayan agency house, Guthrie & Co. This in itself challenges the notion that Britain’s myriad of ‘free-standing’ companies, which were typical of direct investment in the Empire, represented a relatively weak and unsustainable form of multinational enterprise. But Hay’s dominance of the Malayan plantation sector also questions the notion of ‘gentlemanly capitalism’ as the driving force behind the expansion and sustenance of the British imperial system. Hay’s network of colonial corporate influence did not extend into the corridors of ‘gentlemanly capitalist’ power in Whitehall and the City, where he often had frosty relations. Ultimately, it was the financial sector in London that brought about Hay’s forced resignation from Guthrie in 1963. Examining questions of class, ethnicity, personality, ideology and strategy, the article focuses on why Hay did not develop better relations with commercial, financial and official elites, issues that would also engender tensions with the post-colonial political and business leadership of Malaya/Malaysia

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast

Grade of recurrent in situ and invasive carcinoma following treatment of pure ductal carcinoma in situ of the breast The grade of recurrent in situ and invasive carcinoma occurring after treatment of pure ductal carcinoma in situ (DCIS) has been compared with the grade of the original DCIS in 122 patients from four different centres (The Royal Marsden Hospitals, London and Sutton, 57 patients; Guy's Hospital, London, 19 patients; Nottingham City Hospital, 31 patients and The Royal Liverpool Hospital, 15 patients). The recurrent carcinoma was pure DCIS in 70 women (57%) and in 52 women (43%) invasive carcinoma was present, which was associated with an in situ element in 43. In all, 19 patients developed a second recurrence (pure DCIS in 11 and invasive with or without an in situ element in eight). The majority of invasive carcinomas followed high-grade DCIS. There was strong agreement between the grade of the original DCIS and that of the recurrent DCIS (k = 0.679), which was the same in 95 of 113 patients (84%). The grade of the original DCIS showed only fair agreement with the grade of recurrent invasive carcinoma (k = 0.241), although agreement was stronger with the pleomorphism score of the recurrent carcinoma (k = 0.396). There was moderate agreement, in recurrent invasive lesions, between the grade of the DCIS and that of the associated invasive element (k = 0.515). Other features that showed moderate or strong agreement between the original and recurrent DCIS were necrosis and periductal inflammation. The similarity between the histological findings of the original and subsequent DCIS is consistent with the concept that recurrent lesions represent regrowth of residual carcinoma. In addition, although agreement between the grade of the original DCIS and that of any subsequent invasive carcinoma was only fair, there is no suggestion that low-grade DCIS lesions progress to higher grade lesions or to the development of higher grade invasive carcinoma. This is in agreement with immunohistochemical and molecular data indicating that low- grade and high-grade mammary carcinomas are quite different lesions