Expression In Breast Cancer Patients Research Articles

Comparison of the Expression of P-Glycoprotein, Ki-67, and P-53 to Technetium-99m Tetrofosmin Mammoscintigraphic Findings

Adjuvant and neoadjuvant chemotherapy is being used increasingly in the treatment of breast cancer patients. However, drug resistance plays an important role in the failure of chemotherapy in breast cancer. The aim of this study was to compare technetium-99m tetrofosmin (Tc-TETRO) mammoscintigraphic findings with the expression of drug resistance proteins (p-glycoprotein [Pgp], Ki-67 and mutant p53) in human breast cancer tissues. Thirty patients diagnosed with infiltrating ductal breast cancer underwent Tc-TETRO mammoscintigraphy before surgery or biopsy. Protein expression was investigated by immunohistochemical analyses on multiple nonconsecutive sections from surgery or biopsy specimens. Tumor to background (T/B) ratios calculated by Tc-TETRO mammoscintigraphic findings were correlated with protein expression determined by immunohistochemical analyses. The Tc-TETRO T/B ratios were significantly lower for tumors in 12 patients with positive Pgp expression than for those in 18 patients with negative expression (1.19±0.13 and 1.94±0.33, p value<0.01). However, differences in Tc-TETRO T/B ratios between the patients with positive and negative Ki-67 or mutant p53 expression were not found in this study. Our data confirmed that Tc-TETRO mammoscintigraphic findings are useful for determination of the presence of Pgp expression in breast cancer patients, but no significant relations between Tc-TETRO mammoscintigraphic findings and Ki67 or mutant p53 were found.

HER-2/neu in Breast Cancer: Interobserver Variability and Performance of Immunohistochemistry with 4 Antibodies Compared with Fluorescent In Situ Hybridization

The immunohistochemistry (IHC) performance of 4 anti-HER-2/neu antibodies was compared with fluorescent in situ hybridization (FISH) analysis of HER-2/neu gene expression in breast cancer patients considered for Herceptin (Trastuzumab) therapy. Interobserver variability in IHC interpretation was measured. Formalin-fixed tissue was received from 24 provincial hospital laboratories. The following anti-Her-2 antibodies were used: DAKO A0485 (polyclonal), Novacastra CB11 (monoclonal), Zymed TAB250 (monoclonal), and DAKO HercepTest (polyclonal). Additional sections were analyzed by FISH (Vysis). Three pathologists blinded to FISH results independently interpreted invasive tumor cell membranous staining on a scale of 0 to +3. The HER-2/neu gene was considered amplified when the FISH signal ratio of HER-2/CEP-17 was ≥2.0. Blocks from all hospitals and of all ages were suitable for IHC and FISH analysis. No interlaboratory analysis variability was noted. The interobserver agreement (kappa) for stain intensity for each antibody was good for 0 and +3 but poor for +1 and +2. Reasonable concordance between IHC and FISH was found with three of the four antibodies. TAB250 was the most sensitive antibody. For the three pathologists, the IHC sensitivities and specificities compared with FISH using 0/+1 as negative and +2/+3 as positive were as follows: A0485, 63–84/95–98; CB11, 63–66/97–98; TAB-250, 82–100/94–95; HercepTest, 59–77/91–93. The positive and negative predictive values varied by stain intensity. Stain scores of 0 and +3 were highly predictive of gene status. Stain scores of +1 and +2 were not sufficiently predictive to classify cases as amplified versus nonamplified. IHC is a reasonable first test to assess HER-2/neu status in patients with breast cancer. For most cases, DAKO A0485, TAB250, and HercepTest adequately predicted gene status. In cases with stain intensity of +1 or +2, the interobserver agreement is poor, and the predictive value is unsatisfactory for clinical use. Additional testing, preferably with FISH, is recommended.

Spontaneous apoptosis of circulating T-lymphocytes and its correlation to their prolactin receptor expression and prolactin plasma levels in patients with breast cancer

We have previously shown that a higher percentage of circulating CD3+ T lymphocytes undergo spontaneous apoptosis in cancer patients as compared with normal controls. Prolactin (PRL) has been reported to inhibit apoptosis in various cell types, including a Nb2 rat lymphoma cell line. In addition, there is evidence that the human PRL-antagonist hPRL-G129R induces apoptosis in breast cancer cell lines. We investigated a possible relationship between prolactin receptor (PRL-R) expression and apoptosis of CD3+ T lymphocytes, as well as PRL plasma levels, in patients with breast cancer. Peripheral blood mononuclear cells of patients (n = 11) and sex-matched normal controls (n = 12) were stained with AnnexinV, anti-Fas mAb (CD95), mouse antihuman PRL-R mAb B6.2, anti-CD3 mAb and respective isotype control mAbs. Multicolor flow cytometry was used to compare expression of these markers on T cell. In patients, 37 ± 19% (median ± SD) of CD3+ cells bound AnnexinV, marking early apoptosis of T lymphocytes compared with 17 ± 10% in controls (P <0.004). Furthermore, 82 ± 15% of the CD3+ T cells were Fas+ in patients, compared with 51 ± 9% in controls (P <0.0001). All CD3+ T lymphocytes were positive for PRL-R expression in breast cancer patients, as well as in normal control individuals. The mean fluorescence intensity of PRL-R on T lymphocytes of breast cancer patients was 106-172 (median 119) compared with 87-176 (median 123), suggesting no difference in PRL-R expression on T lymphocytes in patients versus controls. PRL plasma levels were comparable in patients and normal controls (4.8 ± 3.4 ng/ml versus 9.8 ± 4.6 ng/ml). In concordance with these findings, PRL was not able to inhibit the onset of apoptosis of Jurkat cells, a thymic lymphoma cell line, incubated with Fas cross-linking CH-11 mAb. These results indicate that PRL/PRL-R might not be involved in modulating Fas/Fas ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes, leading to excessive turnover of T cells in the circulation of patients with breast cancer.

Prognostic significance of apoptosis related gene family bcl-2 in human breast cancer

Objective: To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: Expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method, bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis, bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox’s model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer, bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

Inhibition of Emotional Expression in Breast Cancer Patients

To obtain a better understanding of the inhibited emotional expression often reported in breast cancer patients, the authors compared 48 breast cancer patients and 49 healthy women with respect to disturbed emotional processes (alexithymia), emotional disclosure, emotional expression, assertiveness, repression, and distress. The patient group showed significantly more ambivalence over emotional expression, more restraint, and more anxiety than the healthy controls. No differences were found between the 2 groups in alexithymia, expressing emotions in general, or willingness to talk with others about emotions. The image of the breast cancer patient that emerged in the study was that of a person who has conflicting feelings with regard to expressing emotions, is reserved and anxious, is self-effacing, and represses aggression and impulsiveness. These findings suggest that cancer patients' inhibited behavior is a reaction to the disease rather than a reflection of a personality characteristic predisposing an individual to (breast) cancer.

100. Changes in TGFB mRNA expression in breast cancer patients treated with tamoxifen

100. Changes in TGFB mRNA expression in breast cancer patients treated with tamoxifen

Association of lytic effector cell function with high expression of HER-2 expression in breast cancer patients

Association of lytic effector cell function with high expression of HER-2 expression in breast cancer patients

Flow cytometric analysis of tumour infiltrating lymphocyte activation and tumour cell MHC Class I and II expression in breast cancer patients

The primary tumour cells and tumour infiltrating lymphocytes (TILs) of 31 breast cancer patients have been analysed by dual colour flow cytometry to determine whether the phenotype and/or activation status of the TILs bears any relationship to the expression of MHC antigens on the tumour cells. The phenotype and activation status of 5000 TILs were studied using Mabs to CD4, CD8, HLA DR, CD25 (the low affinity inducible IL-2 receptor) and the transferrin receptor and related to Class I and Class II MHC expression on 5000 primary tumour cells. On the tumour cells. Class I MHC expression ranged from 1–74%, averaging 12.9%. HLA DR expression ranged from 1–69% averaging 14.3%. When the phenotypic proportions of the lymphocytic infiltrate were analysed there was found to be a correlation between tumour expression of Class I MHC and the proportion of both CD4+ (P < 0.05) and CD8+ (P < 0.02) T cells within the tumour. No such relationship was found with the MHC Class II antigen. When TIL activation markers were analysed, the percentage of CD8+ TILs positive for HLA DR expression correlated strongly with the expression of Class I (P < 0.001) and Class II (P < 0.001) antigens on the tumour cells. The percentage of CD4+ TILs positive for HLA DR expression also correlated significantly, but less strongly with the expression of Class I (P < 0.01) and Class II (P < 0.02) antigen expression on the tumour cells. The percentage of CD4 + TILs positive for CD25 expression correlated with both Class I (P < 0.05) and Class II (P < 0.03) expression on the tumour cells while the percentage of CD8 + TILs positive for CD25 did not. The percentage of TILs bearing the transferrin receptor showed no measurable correlation with the expression of either class of MHC antigen on the tumour. The data suggest that MHC expression on the tumour cells has a selective effect on the response capacity of different parts of the immune system.

Serum iga and emotional expression in breast cancer patients

As part of a multidisciplinary study of 160 women admitted consecutively for breast tumour biopsy, we measured expression of anger and serum immunoglobulins before operation, when we had no knowledge of the provisional diagnosis, and at 3, 12 and 24 months after operation. Expression of anger was not related to serum IgG, IgM or IgE levels, but IgA levels were found to be significantly higher in patients who habitually suppressed anger than in those who were able to express anger ( p<0·001). This correlation was found before operation both in cancer patients and those with benign breast disease. Over the subsequent two years serum IgA levels remained consistently higher in all patients who suppressed anger, but only reached statistical significance in breast cancer patients 3 months ( p<0·02) and 2 years ( p<0·03) following operation. We suggest how such an association might play a part in the pathogenesis of breast cancer.