Showing papers by "Cheryl Gillett published in 1993"
TL;DR: Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E‐ and P‐cadherin is present in both luminal and myoepithelial cells, whereas P‐ (placental) caderin is confined to myoEPithelium.
Abstract: Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E-(epithelial) cadherin is present in both luminal and myoepithelial cells, whereas P- (placental) cadherin is confined to myoepithelium. There is experimental evidence that loss of E-cadherin is associated with increased invasiveness of malignant cells in vitro, which stimulated us to examine the presence and distribution of E- and P-cadherin in breast carcinomas by means of immunohistochemical staining. E-Cadherin was present in all in situ and invasive ductal carcinomas examined, although it had a patchy distribution and the staining was of variable intensity. However, in 83 per cent of invasive lobular carcinomas and all lobular carcinomas in situ there was complete loss of E-cadherin expression. In the remaining 17 per cent of invasive lobular tumours, E-cadherin appeared to have an abnormal distribution within the cytoplasm with variable expression on the cell membrane. P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type. It was found in only one carcinoma of lobular type. We suggest that loss of cell-cell adhesion mediated by E-cadherin plays a part in the characteristic morphology of lobular carcinomas.
210 citations
TL;DR: The results indicate the absence of clinically important concentrations of oestrogen and progesterone receptors in breast fibromatoses and suggest that treatment directed against oestrogens is unlikely to be beneficial.
Abstract: AIMS--To investigate the oestrogen and progesterone receptor concentrations expressed on mammary fibromatoses to determine their responsiveness to oestrogenic stimuli. METHODS--Six mammary fibromatoses were examined using immunohistochemistry for the presence of oestrogen and progesterone receptors using antibodies against the receptor proteins. Enzyme immunoassays (EIAs) using the same antibodies were also performed in four patients. Immunohistochemical staining for pS2 protein was also carried out as a measure of functional oestrogen receptors. RESULTS--Neither receptor nor pS2 protein was expressed using immunohistochemistry. Very low concentrations of both oestrogen and progesterone receptors were shown by EIA. CONCLUSION--These results indicate the absence of clinically important concentrations of oestrogen and progesterone receptors in breast fibromatoses and suggest that treatment directed against oestrogen is unlikely to be beneficial.
25 citations
TL;DR: In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis, which warrants further investigation as a proliferation-related marker.
Abstract: There is considerable interest in immunohistochemical markers of proliferation which are suitable for use on routinely fixed clinical material. The novel proliferation-associated antibody Ki-S1 shows promise in this respect. In this study we have: (i) defined the pattern of Ki-S1 labelling relative to the cell cycle phase; (ii) investigated the labelling pattern with Ki-S1 on a human breast cell line (ZR75) under varying proliferative conditions induced by serum deprivation and refeeding; (iii) examined in a flow cytometric study Ki-S1 staining in archival, clinical breast carcinoma samples. In exponentially growing cells Ki-S1 showed a marked cell cycle phase-specific variation in staining intensity which increased linearly through the S-phase, was high in G2 and reached its peak in mitosis. Ki-S1 staining intensity mirrored the changes in proliferative activity of ZR75 cells during serum deprivation and refeeding. In a small series of human breast carcinoma, Ki-S1 staining intensity correlated with S-phase fraction (SPF) derived from DNA profiles. The antigen labelled by Ki-S1 is extremely robust, resisting degradation by fixation and by an aggressive enzymic tissue disaggregation method. Ki-S1 warrants further investigation as a proliferation-related marker, particularly for routine clinical application.
25 citations
TL;DR: The staining patterns obtained with two antibodies against proliferating cell nuclear antigen and another cell cycle associated antibody were compared with each other and with a number of established prognostic markers of breast carcinoma, suggesting that the two PCNA antibodies detect different epitopes.
Abstract: The staining patterns obtained with two antibodies against proliferating cell nuclear antigen (PC10 and 19A2) and another cell cycle associated antibody (KiS1) were compared with each other and with a number of established prognostic markers of breast carcinoma. Although PC10 and 19A2 staining patterns were similar, only the latter was significantly associated with KiS1 antibody staining. These findings suggest that the two PCNA antibodies detect different epitopes. KiS1 was the only antibody to show an association with S phase fraction measured by flow cytometry (p < 0.001). It was also associated with histological grade (p = 0.003), oestrogen receptors (p = 0.045), and DNA index (p = 0.007). PC10 showed no association with any of the markers of prognosis, while 19A2 was associated with histological grade (p = 0.017) and oestrogen receptors (p = 0.043). The two PCNA antibodies do not seem to be of value in measuring proliferative activity nor do they seem to be associated with established markers of prognosis in breast cancer.
16 citations
TL;DR: It is demonstrated that two of the main β chains, β1 and β4, can be effectively demonstrated on methacarn and cold (4°C) formalin‐fixed tissues by avidin‐biotin indirect immunoperoxidase staining and that the results are similar to those achieved using frozen tissue.
Abstract: The integrins are alpha beta heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. Previous distribution studies on integrin expression have been limited by the requirement of cryostat sectioned tissues, and consequent poor resolution. We have examined 40 examples of ductal carcinoma in situ (DCIS) for the expression of both beta 1 and beta 4 integrin chains. These showed strong polarized membrane staining of residual myoepithelial cells (correlating with expression of smooth muscle specific actin) and of the basement membrane region with beta 1 and beta 4 antibodies respectively. In 12 out of 40 cases, the DCIS was negative for the beta 1 chain and a variable pattern of reactivity was seen in the remaining cases. The beta 4 chain was detected focally and weakly in the tumour cells of 7/40 DCIS and strongly in one; all of these cases were also positive for the beta 1 chain. Of the 22 cases where co-existent invasion was present, the infiltrating component showed either a similar degree or a diminution of the extent of immunostaining when compared with the in situ component; only one showed enhanced staining (beta 1 only). This study demonstrates that two of the main beta chains, beta 1 and beta 4, can be effectively demonstrated on methacarn and cold (4 degrees C) formalin-fixed tissues by avidin-biotin indirect immunoperoxidase staining and that the results are similar to those achieved using frozen tissue.
16 citations