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S Shousha

Publications and source records attributed to S Shousha.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study.

AIMS: Prolactin plays an important role in the proliferation and differentiation of normal breast epithelium, and possibly in the development of breast carcinoma. The effects of prolactin are mediated by its receptor; thus, alteration in the expression of this receptor could be important in studying the biology of breast cancer. This investigation was aimed at comparing the expression of prolactin receptors in normal, benign, and malignant breast tissue. MATERIAL/METHODS: The expression of prolactin receptors was studied in paraffin wax embedded sections of 102 breast biopsies (93 female and nine male), using the monoclonal antibody B6.2, and the avidin-biotin immunoperoxidase technique. Six biopsies were normal, 34 had benign lesions, and 62 were malignant. RESULTS: In normal cases, prolactin receptor positivity was seen only on the luminal borders of the epithelial cells lining ducts and acini. In most benign lesions, variable degrees of luminal and cytoplasmic staining were seen. Cells showing apocrine metaplasia and florid regular ductal epithelial hyperplasia were mostly negative. In malignant cases, the staining pattern was mostly cytoplasmic and heterogeneous. Forty one of the 59 carcinomas in women showed a degree of positivity involving 10-100% of the tumour cells. A significant direct correlation was found between prolactin receptor and oestrogen receptor staining when only cases that scored more than 100/300 for the latter receptor, using the H scoring system, were considered (p = 0.0207). No correlation was found between prolactin receptors and progesterone receptors, patient's age, tumour size, tumour grade, or axillary lymph node status. CONCLUSIONS: Prolactin receptors seem to be expressed at different cellular sites in normal, benign, and malignant breast epithelial cells. The receptor is expressed in more than two thirds of female breast carcinomas, suggesting that it may play a role in the pathogenesis of the disease. The positivity is correlated with moderate and strong staining for oestrogen receptors in tissue sections, but not with other prognostic factors.

Adult↗
PubMed2001

Multifocal squamous cell carcinoma of the oesophagus following radiotherapy for bilateral breast carcinoma.

A 60 year old woman who presented with dysphagia and weight loss was found to have multiple foci of dysplasia and in situ and invasive squamous cell carcinoma scattered along the whole length of the oesophagus, with intervening areas of normal mucosa. The patient had a history of two breast carcinomas 19 and one year previously for which she had repeated radiotherapy. Several members of the patient's close family had histories of malignant disease. All oesophageal lesions and the more recent breast cancer showed positive immunostaining for p53 protein. p53 mutations, some involving different exons, were also detected in these lesions. No p53 immunostaining or mutations were detected in the normal oesophageal mucosa. The findings suggest an independent origin of the multiple dysplastic and neoplastic foci, which might have developed in a background of a field change, possibly related to the previous radiotherapy. The strong family history of malignant diseases raises the possibility that, in addition, genetic factors might have played a role in the development of the oesophageal disease.

Breast Neoplasms↗
PubMed2001

Comparison of immunoperoxidase staining of 3 different types of CD5 antibodies in a spectrum of breast lesions.

CONTEXT: We recently described a patient with chronic lymphocytic leukemia who presented with a breast carcinoma that stained positive for CD5 using a commercially available antibody (CD5-4C7, Novocastra, Newcastle upon Tyne, UK). OBJECTIVES: To study the distribution of CD5 immunoreactivity in tissue sections of a variety of benign and malignant breast lesions using the antibody CD5-4C7 and to compare the results with those obtained with 2 other commercially available CD5 antibodies (CD5/54/F6, Dako, Ely, Cambridgeshire, UK, and CD5/54/B4, Novocastra). DESIGN: Paraffin sections of 102 breast biopsy specimens with various diagnoses were examined using the avidin-biotin immunoperoxidase complex technique. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: The staining results obtained with CD5-4C7 were different from those obtained with the other 2 antibodies. With 4C7, the normal and benign biopsy specimens showed varying numbers of positive epithelial cells and lymphocytes. Heterogeneous positive staining was also present in 47 (78%) of 60 invasive female breast carcinomas and in all 3 male breast carcinomas examined. A statistically significant correlation was found between CD5 positivity and tumor grade, with grade 3 tumors being less likely to be CD5 positive than grades 1 and 2 (P =.0035). No correlation was found between CD5 positivity and patient's age, tumor histologic type, axillary lymph node status, or progesterone receptors. On the other hand, the CD5/54/F6 and CD5/54/B4 antibodies only stained lymphocytes and occasional normal breast ducts, mostly those showing apocrine metaplasia. All other normal benign and malignant epithelial cells were negative. CONCLUSIONS: Positive staining for CD5 using the antibody 4C7 is seen in normal and benign breast tissue and 78% of invasive breast carcinomas. The positivity is more common in low-grade tumors. No significant staining was seen with the 2 other CD5 clones used in this study. The significance of the positive staining obtained with CD5-4C7 is not obvious, but this clone may be more sensitive than the others, or it may be recognizing an epitope shared by another antigen.

Antibodies↗
PubMed2000

Breast carcinoma presenting during or shortly after pregnancy and lactation.

CONTEXT: Much has been written about the clinical management and prognosis of breast carcinomas presenting during pregnancy and lactation, yet little is known about the detailed histopathology of these tumors. OBJECTIVE: To determine whether these carcinomas have any specific diagnostic features. DESIGN: A detailed histologic and immunohistochemical study of 14 cases of breast carcinoma presenting during or shortly after pregnancy or lactation was conducted. The findings were compared with a control group of 13 tumors developing in age-matched women with no recent history of pregnancy or lactation. SETTING: The histopathology department of a tertiary referral teaching hospital. RESULTS: Tumors in the pregnancy/lactation group had a significantly higher incidence of cancerization of lobules (79% vs 15%) and of grade III invasive ductal carcinomas (80% vs 33%). Tumors occurring during lactation were either totally or partly mucinous and were MUC2 positive. Tumors occurring during pregnancy, but not during lactation, were mostly estrogen and progesterone receptor negative (4/5 and 5/5, respectively). All tumors occurring during pregnancy and lactation that were tested for c-erbB-2 overexpression were negative, whereas all 4 tumors tested that occurred shortly after delivery or cessation of lactation were positive for c-erbB-2 overexpression. The incidence of axillary lymph node metastasis was high in both the study and control groups, although it was slightly higher in the control group (78% and 90%, respectively). CONCLUSIONS: Although breast carcinomas diagnosed during or shortly after pregnancy and lactation have features in common with those developing in women of similar ages, particularly with respect to a high incidence of lymph node metastasis, the findings of this study suggest that they may also have distinct morphologic and immunohistochemical features of their own. Such features may vary according to whether the patient was pregnant, lactating, or had recently terminated her pregnancy or lactation at the time of surgical excision. Examination of more cases would help confirm these findings.

Adult↗
PubMed1999

Primary tumour characteristics and axillary lymph node status in breast cancer.

This paper examines the correlation between axillary lymph node status and primary tumour characteristics in breast cancer and whether this can be used to select patients for axillary lymphadenectomy. The results are based on a retrospective analysis of 909 patients who underwent axillary dissection in our unit. Axillary lymph nodes containing metastases were found in 406 patients (44.7%), all with invasive carcinomas, but in none of the 37 carcinomas-in-situ. Nodal status was negative in all T1a tumours, but lymph node metastases were present in 16.3% and 35.7% of T1b and T1c tumours respectively. When histological grade was taken into account, positivity for grade I T1b and T1c tumours fell to 13.6% and 26.7% respectively. Lymph node metastases were found in 85% of patients with lymphovascular invasion in their tumours as compared to only 15.4% of those without and in 45.5% of oestrogen and progesterone receptor-positive tumours. When one or both hormone receptors were absent this figure was much higher. It appears that for T1a breast cancers axillary dissection is not necessary, whereas for T1b, T1c and grade I T2 tumours other histopathological parameters should be taken into consideration in deciding who should undergo axillary lymphadenectomy.

Breast Neoplasms↗
PubMed1999

Adenoid cystic carcinoma of the breast: a tumour commonly devoid of oestrogen receptors and related proteins.

AIM: Adenoid cystic carcinoma (ACC) of the breast is an uncommon well-differentiated tumour with good prognosis, and sometimes difficult to distinguish from in-situ and invasive cribriform carcinoma (ICC) which are relatively more common. Recently, we encountered a case of ACC that proved to be totally oestrogen receptor (ER) negative by immunohistochemistry. We investigated the possibility that this may be a consistent feature that can help in differentiating ACC from ICC which are usually ER positive. METHODS AND RESULTS: The immunoperoxidase technique was used to study the expression of ER and other related proteins in six cases of ACC and two cases of ICC. All ACC cases were negative for oestrogen (ER) and progesterone (PgR) receptors whereas the two ICC were strongly positive for ER and showed a variable degree of PgR positivity. In addition, ACC cases were pS2 negative and showed minimal expression of prolactin receptors (PrlR), while the two ICC showed widespread and strong staining for pS2 and PrlR. The percentages of cells staining positively for Ki67 and p27 were generally lower in ACC than in ICC. Both tumour types were c-erbB-2 negative, but p53 was weakly to moderately positive. CONCLUSIONS: The findings suggest that a negative immunoperoxidase staining for ER would confirm the diagnosis of ACC in contrast to the positive staining which is always seen in ICC. The findings also raise the issue of the presence of a specific class of ER negative breast carcinomas which are negative not because of poor differentiation, but because of their derivation from, or differentiation along, an ER negative cell lineage.

Adenocarcinoma↗
PubMed1998

An important role for BRCA1 in breast cancer progression is indicated by its loss in a large proportion of non-familial breast cancers.

The presence of BRCA1 protein was determined immunohistochemically in normal and benign breast biopsies, non-familial breast carcinomas and breast carcinomas from one or more individuals from 8 BRCA1 families. Strikingly, little staining was detected in breast carcinomas from BRCA1 families, regardless of the position or type of mutation, whereas strong immunostaining was observed in 28/28 of non-malignant breast biopsies. Furthermore, BRCA1 staining was reduced in non-familial breast carcinomas, since loss of nuclear BRCA1 staining was evident in 19% of non-familial breast carcinomas whilst a similar proportion (20%) showed absence of either cytoplasmic or nuclear BRCA1 staining. Statistical analysis indicates that breast cancer is characterised by a reduction in levels of nuclear BRCA1 in familial (p < 0.001) and non-familial breast cancer (p = 0.001). In non-familial breast cancer absence of nuclear BRCA1, but not cytoplasmic BRCA1, is more common in high grade breast carcinomas (p = 0.03) and in patients with evidence of lymph node involvement (p = 0.05). Correlation between the absence of BRCA1 protein with high grade is consistent with previous findings of a correlation between mutations in the BRCA1 gene and high grade. Our findings provide new evidence in support of BRCA1 as a tumour suppressor protein in non-familial breast cancer.

Adult↗
PubMed1998

Breast carcinoma in women under the age of 50: Relationship between p53 immunostaining, tumour grade, and axillary lymph node status.

There is evidence to suggest that breast carcinoma in young women behaves in a more aggressive manner than in older women. As positive immunostaining for p53 has also been associated with increased tumour aggressiveness, this study was aimed at finding out whether patients under the age of 50 years have a higher prevalence of p53 positivity in their tumours. The inter-relationships between age, p53, tumour grade, and axillary lymph node status were also investigated. Two hundred and twenty nine invasive carcinomas were studied. One hundred and eight patients were under the age of 50, and 121 were at or above that age. The specific p53 monoclonal antibody DO7 and the avidin-biotin complex immunoperoxidase technique were used. Fifty seven tumours (25 %) showed variable degrees of p53 positivity. The incidence of positivity was slightly higher in women under the age of 50 as compared with those at or above that age (29% (31/108) vs. 21% (26/121), respectively), but the difference was not statistically significant (p < 0.05). On the other hand, in invasive ductal carcinoma (191 cases), p53 positivity was significantly related to high tumour grade (7% in grade I [1/14], 19% in grade II [20/105], and 43% in grade III [31/72]; p < 0.0001 [I-II vs III]). p53 positivity was also significantly related to the presence of extensive (more than three) axillary lymph node metastases (p53 positivity being 22% in node negative tumours [40/178], 18% in tumours with three or less positive nodes [6/33], and 61% in tumours with more than 3 positive nodes [11/18]; p = 0.0033 [second vs third group]). Both features were also significantly more common in the younger age group. The results suggest that the slightly higher incidence of p53 positivity seen in tumours from younger patients, is probably related to the significantly higher incidence of grade III tumours in these patients.

Adult↗
PubMed1998

CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic leukaemia: molecular studies of chromosome 13q.

A 67 year old woman presented with a right breast lump which proved to be a grade 2 invasive ductal carcinoma with axillary lymph node metastasis. She had a five year history of CD5 positive chronic lymphocytic leukaemia, which never required treatment. Immunoperoxidase stains for CD5, using the monoclonal antibody NCL-CD-54C7, showed that there was extensive infiltration of axillary lymph nodes with CD5 positive B lymphocytes. Strong staining for CD5 was also seen in the carcinoma cells within the breast and lymph node metastases. It has recently been suggested that there is a tumour suppresser locus in chronic lymphocytic leukaemia at 13q12.3 near or at the BRCA2 locus. Deletion of regions on chromosome 13q containing the BRCA2 and RB1 genes has also been reported in sporadic breast cancers. These observations suggest that there may be a link between these two diseases acting through chromosome 13, but amplification of several microsatellite repeat markers failed to show any loss of heterozygosity or repeat instability at either these or several other loci on chromosome 13. Examination of additional such cases is needed to perform a more comprehensive study of the significance of positive CD5 staining of breast carcinoma.

Aged↗
PubMed1998

Breast carcinoma developing in patients on hormone replacement therapy: a histological and immunohistological study.

AIM: To study the histopathological features of breast carcinoma developing in postmenopausal patients on hormone replacement therapy (HRT). METHODS: The sample comprised 60 patients with invasive breast carcinoma including 31 who had received HRT at or shortly before presentation, and 29 who had not. Details concerning their tumour size, histological type and grade, lymph node status, and oestrogen and progesterone receptor status were compared. Immunoperoxidase staining for Bcl-2, p53, and E-cadherin was carried out on paraffin sections of all 60 patients. The results were then statistically analysed. RESULTS: Tumours detected in HRT patients were significantly smaller (mean 17 mm v 25 mm; p = 0.0156) and of a lower histological grade (p = 0.0414) than those detected in non-HRT patients. The incidence of invasive lobular carcinoma was slightly higher in HRT patients (19% v 14%). Immunohistologically, 87% of HRT tumours were Bcl-2 positive (compared with 79% in the control group), 29% were p53 positive (45% in the control), and 48% were E-cadherin positive (72% in the control group). Although the differences were not statistically significant there was a trend towards higher incidence of p53 negative and E-cadherin negative tumours in HRT patients. CONCLUSIONS: Breast carcinomas detected in patients on HRT have a significantly higher incidence of two favourable prognostic features (small size and a low histological grade). They also show a trend, statistically not significant, of being p53 negative and E-cadherin negative; this may be related to the slightly higher incidence of invasive lobular tumours in these patients.

Breast Neoplasms↗
PubMed1997

High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers.

The expression of cyclin-dependent kinase inhibitor p27(kip1) in human tumors and normal tissues was investigated using a panel of novel anti-p27(kip1) mAbs. An inverse correlation between expression of p27(kip1) and cell proliferation was generally observed after analyzing its expression in 25 different normal human tissues. In some highly proliferative human breast cancer cells, however, high level p27(kip1) expression was seen, indicating the existence of a mechanism by which some growing tumor cells may tolerate this inhibitor of cell cycle progression. Detailed studies demonstrated a correlation between the high level expression of p27(kip1) and cyclin D1 in human breast cancer cells. There was also an inverse correlation between the expression of p27(kip1) and the degree of tumor malignancy in human breast and colorectal cancers, indicating that p27(kip1) may be a useful prognostic marker in these cancers.

Biomarkers, Tumor↗
PubMed1997

Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance.

A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-109). We have examined the expression of the exon 5-deleted ER (HE delta5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT - PCR). HE delta5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% CI, P=0.05). Presence of the HE delta5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HE delta5 and disease-free survival (P=0.05), suggesting that the presence of HE delta5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HE delta5. This antibody recognized the variant but not the wild-type ER protein. We show that HE delta5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HE delta5 in mammalian cells and showed that, in MCF-7 cells, HE delta5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer.

Adult↗
PubMed1997

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue.

Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 37 degrees C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.

Animals↗
PubMed1997

Fibroblast growth factor 2 in breast cancer: occurrence and prognostic significance.

This paper examines the expression of fibroblast growth factor 2 (FGF-2) in the malignant human breast. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the level of expression of FGF-2 in a series of 51 patients clinically followed up for a median of 84 months (Luqmani et al, 1992). Immunohistochemistry and Western blotting were used to show that the level of FGF-2 in breast tissues correlated with the amount of FGF-2 mRNA. FGF-2 was present in both malignant and non-malignant breast, although less was expressed in malignant tissues as determined by all three methods. Immunohistochemistry on frozen sections of breast tissue showed expression of FGF-2 in myoepithelial and epithelial cells in non-malignant samples and generally lower or undetectable levels of staining in malignant epithelial cells. The results obtained by immunohistochemistry correlated well with RT-PCR data showing similar levels of FGF-2 and FGF-2 mRNA expression in samples. No correlation was found between FGF-2 mRNA expression and T stage, nodal status or oestrogen receptor status. However, Kaplan-Meier survival plots show that higher levels of FGF-2 are associated with improved overall and disease-free survival. We suggest that FGF-2 expression may have value as a prognostic indicator in breast cancer.

Adult↗
PubMed1997

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer.

Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting the normal breast. Moreover, breast cancer cells lack one form of FGFR-1. Western blot analysis showed 115-kDa and 106-kDa forms of FGFR-1 within the human breast. The 115-kDa band corresponds to the beta form of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl terminus. The 106-kDa form of FGFR-1 is the major form present in breast fibroblasts and myoepithelial cells, whereas epithelial cells contain equal amounts of the 115-kDa and 106-kDa forms. Breast cancer cells, however, appear to contain only the 115-kDa form of FGFR-1. This expression pattern is reflected in malignant and non-malignant tissue samples. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, we have shown that the 106-kDa FGFR-1 isoform is not the previously described alpha 2 receptor that arises from a 25-base pair insertion in the second kinase domain. It is probable that the 106-kDa FGFR-1 has different signalling properties to the full-length receptor, having lost at least one tyrosine at amino acid 766, which is required for phospholipase C activation. This form of FGFR-1 appears to be lost in all breast cancer cells analysed and its absence may have a bearing on malignancy.

Amino Acid Sequence↗
PubMed1997

Oestrogen and progesterone receptor assessment in core biopsy specimens of breast carcinoma.

AIMS: To assess the suitability of core biopsy specimens for the immunohistological assessment of oestrogen and progesterone receptors in breast carcinoma. METHODS: Thirty consecutive cases of clinically palpable breast carcinoma, from which both core and excision biopsy specimens were available, were examined. Routinely processed paraffin wax sections were stained using the specific monoclonal antibodies 1D5 (Dako) for oestrogen receptor and NCL-PGR (Novocastra) for progesterone receptor, after an antigen retrieval step using a pressure cooker. Staining results were assessed using the H score system with the results being expressed as negative, weakly positive, moderately positive or strongly positive. RESULTS: Twenty six biopsy specimens contained enough tumour tissue for assessment. Absolute agreement between scoring categories was seen in 19 (73%) cases for oestrogen receptors. However, when all positive categories were added together, agreement between core and excision biopsy specimens increased to 93% (24 cases). Disagreement was seen only in two cases which stained positive in the core biopsy specimens and negative in the excision biopsy specimens. For progesterone receptors, the absolute agreement between all scoring categories was seen only in 11 (42%) cases. When all positive categories were considered together, agreement increased to 69% (18 cases). Five cases were progesterone receptor positive in core but not in excisional biopsy specimens, while three cases were negative in core but positive in excisional biopsy specimens. CONCLUSIONS: The results suggest that core biopsy specimens can be reliably used for oestrogen receptor assessment, but are less reliable for progesterone receptor assessment, probably because of a greater heterogeneity of progesterone receptor staining.

Biopsy↗