Prognostic value of HER3, PTEN and p-HER2 expression in patients with HER2positive breast cancer.

BACKGROUND: HER2 overexpression is an unfavorable prognostic factor in patients with breast cancer, but it is also a target for the monoclonal antibody trastuzumab, which is effective in adjuvant and palliative settings. HER2 positivity is an inclusion criterion for immunotherapy, but it is not a positive predictive factor, and only half of patients benefit from the treatment. AIM: The aim of this study was to evaluate the prognostic and predictive value of HER3, PTEN and phosphorylated HER2 (p-HER2) expression in primary breast tumors of patients treated with trastuzumab in an adjuvant or palliative regimen. MATERIAL/METHODS: Immunohistochemical (IHC) analysis with 3 antibodies specific to the proteins was performed in tumor specimens obtained from 81 HER2-positive patients treated with trastuzumab. RESULTS: HER3 overexpression was present in 55.6% of the examined tumors, and PTEN or pHER2 positivity was present in 32.0% and 34.6% of them, respectively. HER3 overexpression and PTEN positivity correlated with larger tumor size (p=0.016 and p=0.008, respectively). p-HER2 positivity correlated with more advanced clinical stage of the disease (p=0.032). There was no correlation between the proteins' expression and survival for 31 patients treated with trastuzumab in the palliative regimen. DISCUSSION: HER3 overexpression, PTEN positivity and p-HER2 positivity in tumor cells of HER2-positive patients correlate with more advanced clinical stage of breast cancer. Expression of these proteins does not predict outcome of trastuzumab treatment.

HER2 molecular subtype is a dominant subtype of mammary Paget's cells. An immunohistochemical study.

AIMS: To test the hypothesis that the similarity of the molecular subtypes of Paget's cells to the molecular subtypes of the underlying breast carcinomas favours the epidermotrophic theory of the origin of Paget's cells. METHODS AND RESULTS: The immunohistochemical expression of markers that define particular molecular subtypes of breast carcinomas were analysed. The whole analysis was performed by means of tissue microarrays in mammary Paget's disease and in the underlying breast carcinoma(s). Human epidermal growth factor receptor type 2 (HER2)-overexpression subtype [oestrogen receptor (ER(-) ); HER2(+) ] was a dominant molecular subtype of Paget's cells (37 of 43 analysed cases; 86%). Luminal B (ER(+) ; HER2(+) ) and luminal A (ER(+) ; HER(-) ) subtypes were identified in 12% and 2% of cases, respectively. None of the analysed tumours presented a basal-like phenotype. A similar distribution of molecular subtypes was identified in the underlying in situ breast carcinomas (HER2 subtype, 82%; luminal A, 6%; luminal B, 6%; basal-like, 6% of cases) and in the invasive component (HER2 subtype, 84%; luminal A, 8%; luminal B, 8%; basal-like, 0% of cases). CONCLUSIONS: HER2 molecular subtype is the dominant, but not the sole subtype seen in Paget's cells of the nipple. A similar distribution of molecular subtypes in both Paget's cells and in the underlying carcinomas strongly suggests their common origin.

Does vimentin help to delineate the so-called 'basal type breast cancer'?

BACKGROUND: Vimentin is one of the cytoplasmic intermediate filament proteins which are the major component of the cytoskeleton. In our study we checked the usefulness of vimentin expression in identifying cases of breast cancer with poorer prognosis, by adding vimentin to the immunopanel consisting of basal type cytokeratins, estrogen, progesterone, and HER2 receptors. METHODS: 179 tissue specimens of invasive operable ductal breast cancer were assessed by the use of immunohistochemistry. The median follow-up period for censored cases was 90 months. RESULTS: 38 cases (21.2%) were identified as being vimentin-positive. Vimentin-positive tumours affected younger women (p = 0.024), usually lacked estrogen and progesterone receptor (p < 0.001), more often expressed basal cytokeratins (<0.001), and were high-grade cancers (p < 0.001). Survival analysis showed that vimentin did not help to delineate basal type phenotype in a triple negative (ER, PgR, HER2-negative) group. For patients with 'vimentin or CK5/6, 14, 17-positive' tumours, 5-year estimated survival rate was 78.6%, whereas for patients with 'vimentin, or CK5/6, 14, 17-negative' tumours it was 58.3% (log-rank p = 0.227). CONCLUSION: We were not able to better delineate an immunohistochemical definition of basal type of breast cancer by adding vimentin to the immunopanel consisted of ER, PgR, HER2, CK5/6, 14 and 17 markers, when overall survival was a primary end-point.

Prognostic relevance of cyclin E expression in operable breast cancer.

BACKGROUND: Cyclin E is an important regulator of cell-cycle progression. High levels of cyclin E protein in breast cancer have been reported in association with higher disease stage, poor histological differentiation of tumor, and lack of steroid receptors. Data concerning the prognostic relevance of cyclin E expression in breast cancer are conflicting. The aim of this retrospective study was to evaluate the prognostic relevance of cyclin E expression assessed by immunohistochemistry in patients with operable invasive ductal breast cancer. MATERIAL/METHODS: The expression of cyclin E was analyzed by immunostaining in 174 women with breast cancer after radical mastectomy with a median follow-up period of 58 months. Tumor samples were judged to be negative (<2%) or positive (> or =2%) according to the percentage of cells showing the nuclear staining pattern. Ninety-nine (56.9%) tumor samples were regarded as cyclin E-positive. RESULTS: Positive staining for cyclin E determined poor prognosis compared with cyclin E-negative patients in all cases (five-year cancer-specific survival rate of 64.5 vs. 84.5%, p=0.005), in the node-positive group (50.9 vs. 82.1%, p=0.008), and in patients treated with adjuvant chemotherapy (71.0 vs. 96.6%, p=0.008). In a multivariate analysis, high expression of cyclin E was associated with a higher risk of death in the node-positive group (hazard ratio: 3.2, 95%CI: 1.3-8.2, p=0.015). CONCLUSIONS: It was demonstrated that a high expression of cyclin E measured by immunohistochemistry was a significant factor of poor prognosis, especially in the node-positive group.

Primary uterine rhabdomyosarcoma in a patient with a history of breast cancer and gastrointestinal stromal tumor.

We describe a unique case of a 67-year-old patient with primary uterine rhabdomyosarcoma with a history of breast cancer and gastrointestinal stromal tumor of the stomach. Uterine rhabdomyosarcoma was diagnosed in our patient during adjuvant treatment of breast cancer with anastrozole. To the best of our knowledge, the development of primary uterine rhabdomyosarcoma has never been described in patients treated with anastrozole. Due to the suggested causative role of tamoxifen in the development of uterine sarcomas, it is interesting to analyze whether the new drug, anastrozole, exerts any pathogenic effect on the development of uterine sarocomas.

Recurrence of cholangiogenous carcinoma in port-sites two years after laparoscopic removal of noncancerous gallbladder.

We present a unique case of carcinoma diagnosed in port-site, two years after uncomplicated laparoscopic cholecystectomy for benign cholecystitis. Analysis of morphology and cytokeratin profile (CK19+ and CK20+/-) of resected port-site tumor allows us to establish the diagnosis of tubular carcinoma with probable cholangiogenic origin. The primary carcinoma was not diagnosed in archival gallbladder tissue, despite repeated histological examination. No other primary tumor was identified during follow-up. Patient history and histological/immunohistochemical picture of the recurrent tumor suggested that primary carcinoma was probably located in the gallbladder, but was not detected during initial and repeated histological examinations of postoperative specimen. The patient is still alive, 12 months after the first port-site recurrence and 36 months after initial laparoscopy.

Relationship of P-cadherin expression to basal phenotype of breast carcinoma.

BACKGROUND: P-cadherin (P-CD) is a molecule expressed mainly by basal cells involved in cell adhesion. We evaluated expression of P-CD in operable breast carcinomas and its relationship with immunohistochemical markers of the basal-like phenotype and with clinical outcome. MATERIAL AND METHODS: Expression of P-CD was analyzed by immunohistochemistry in 194 tissue specimens of invasive operable ductal breast cancer. RESULTS: 112 cases (57.7%) were identified as being P-CD-positive. P-CD-positive tumors usually lacked steroid receptors (p = 0.042), expressed basal type cytokeratins (p = 0.001), and were positive for cyclin E (p = 0.039). In a univariate analysis of cancer-specific survival with a median follow-up period of 58 months, P-CD expression was not associated with prognosis (5-year survival rate for positive vs. negative patients 67.0 vs. 77.0%, log rank p = 0.121). CONCLUSION: P-CD may be regarded as an additional immunohistochemical marker of basal-like breast carcinomas. However, P-CD expression is not an adverse prognostic factor.

[Breast neoplasm in men and women--prognosis comparison]. / Rak piersi u mezczyzn i u kobiet--porównanie rokowania.

UNLABELLED: Male breast cancer is a rare disease, therefore our knowledge of the disease is limited. AIM: Comparison of prognosis of male breast cancer and not-otherwise specified (NOS) invasive ductal female breast cancer and invasive lobular female breast cancer. MATERIAL AND METHODS: From 1.01.1997 to 31.03.2000 in Clinical Department of Surgical Oncology, Medical University of Lódz, 3862 patients were operated on breast cancer. There were 24 males (0.6%) and 3838 females (99.4%). Full clinical and pathological data concerning 22 males were collected; these males composed a studied group. Females with invasive lobular breast cancer (65 women) and with invasive ductal NOS breast cancer (474 women) operated on in our Department from 1977 to 1982 composed comparison groups. P-value of = 0.05 was considered as statistically significant. RESULTS: Comparison of survival between males with breast cancer and females with invasive ductal NOS breast cancer: Gehan-Wilcoxon test P = 0.914; Mantel-Cox test P = 0.825; log-rank test P = 0.865; Peto-Peto test P = 0.901. Comparison of survival between males with breast cancer and females with invasive lobular breast cancer: Gehan-Wilcoxon test P = 0.443; Mantel-Cox test P = 0.305; log-rank test P = 0.413; Peto-Peto test P = 0.421. CONCLUSION: Prognosis of male breast cancer is not statistically different from that of female invasive ductal NOS and invasive lobular breast cancer.