Heat shock protein gp96 and CD4+ and CD8+ T-lymphocytes expression as prognostic factors in various molecular types of invasive breast carcinoma.

Breast carcinoma shows extensive clinical and molecular heterogenicity. Glycoprotein gp96 is considered a negative prognostic and predictive factor. Controversy exists over the prognostic role of tumor lymphocytic infiltrates. The goal of this study is to illustrate differences in gp96 and CD4+ and CD8+ T-lymphocytes expression among all immunohistochemical groups of breast carcinoma in relation to the clinical course and outcome of the disease. A retrospective observational study was conducted through processing and analysis of 152 female patient tissue samples previously classified by immunohistochemistry. After immunohistochemical processing, the samples were microscopically analyzed and positive cells were manually calculated in the entire biopsy sample for each patient. In the group of patients with triple negative carcinoma, a significantly higher number of CD4 positive cells in patients with no local recurrence were proven, as well as a significant correlation between a smaller number of CD4 positive cells with a lethal outcome. In the group of patients with Luminal B HER2+ carcinoma, a significantly higher proportion of CD8+ cells in patients with local recurrence were demonstrated. The highest glycoprotein gp96 expression was demonstrated in the group of patients with triple negative carcinoma, while the lowest in patients with Luminal A and Luminal B HER2- carcinoma. This study has shown significantly higher gp96 expression and higher extent of tumor lymphocytic infiltrate in more malignant types of breast carcinoma and represents a significant contribution in affirmation of the prognostic role of these variables.

"V"-technique as a method of breast conserving surgery in multifocal and T2 invasive breast cancers situated in the upper outer quadrant / La técnica "V" como método quirúrgico para conservar las mamas en cánceres de mama invasivos T2 y multifocales situados en el cuadrante superior externo

OBJECTIVE: To assess the oncologic and cosmetic outcomes in women with multifocal breast cancers or T2 tumours with diameters larger than 3 cm situated in the upper outer quadrant who were treated with "V"-technique. METHODS: From July 1999 till June 2003, 44 conserving surgeries with "V"-technique using a local rotational flap were performed. Localization of tumours was in the upper outer quadrant. All solid tumours were larger than 3 cm in diameter. In all patients, axillary lymph node dissection was performed. All the patients received postoperative radiotherapy. Mean follow-up was 58 months. RESULTS: Out of 44 conserving surgeries with "V"-technique, an adequate distance of tumour from the margins was obtained in 84.1% (37/44). Out of 37patients who underwent conserving surgery with this technique, the cosmetic result was favourable in 83.78% (31/37). None of these patients had a corrective surgery such as reduction mammaplasty or mastopexy. Mean weight of excised tissue was 215 g. The 5-year local recurrence rate was 10.8%. The 5-year metastasis-free survival rate was 81,1%. The 5-year overall survival rate was 86.5 %. CONCLUSIONS: Surgical treatment of multifocal and T2 breast cancers larger than 3 cm in diameter situated in the upper outer quadrant and performed with "V"-technique gives a good aesthetic result and enables a wide resection of breast tissue around the tumour.

OBJETIVO: Evaluar los resultados oncológicos y cosméticos en las mujeres con cánceres multifocales de mama o tumores T2 de diámetro mayor de 3 cm, situados en el cuadrante superior externo, en pacientes tratadas con la técnica "V". MÉTODOS: De julio 1999 hasta junio de 2003, se realizaron 44 cirugías conservadoras usando la técnica "V" con colgajo local de rotación. Los tumores se hallaban localizados en el cuadrante superior. Todos los tumores sólidos tenían más de 3 centímetros de diámetro. A todas las pacientes se les practicó la disección del ganglio linfático axilar. Todas las pacientes recibieron radioterapia postoperatoria. El seguimiento promedio fue de 58 meses. RESULTADOS: De las 44 cirugías conservadoras con la técnica "V", se obtuvo una distancia adecuada del tumor en 84.1% (37/44) desde los márgenes. De 37 pacientes que tuvieron cirugía conservadora con esta técnica, el resultado cosmético fue favorable en 83.78% (31/37). A ninguna de estas pacientes se les realizó cirugías correctivas tales como mamoplastia de reducción, o mastopexia. El peso promedio del tejido extirpado fue 215 g. La tasa de recurrencia local quinquenal fue de 10.8%. La tasa de supervivencia quinquenal libre de metástasis fue 81, 1%. La tasa general de supervivencia fue de 86.5%. CONCLUSIONES: El tratamiento quirúrgico de los cánceres de mama T2 y multifocales mayores de 3 cm. de diámetro situados en el cuadrante superior externo y realizado con la técnica "V" produce un buen resultado estético y permite una resección amplia del tejido mamario alrededor del tumor.

"V"-technique as a method of breast conserving surgery in multifocal and T2 invasive breast cancers situated in the upper outer quadrant.

OBJECTIVE: To assess the oncologic and cosmetic outcomes in women with multifocal breast cancers or T2 tumours with diameters larger than 3 cm situated in the upper outer quadrant who were treated with "V"-technique. METHODS: From July 1999 till June 2003, 44 conserving surgeries with "V"-technique using a local rotational flap were performed. Localization of tumours was in the upper outer quadrant. All solid tumours were larger than 3 cm in diameter In all patients, axillary lymph node dissection was performed. All the patients received postoperative radiotherapy. Mean follow-up was 58 months. RESULTS: Out of 44 conserving surgeries with "V"-technique, an adequate distance of tumour from the margins was obtained in 84.1% (37/44). Out of 37 patients who underwent conserving surgery with this technique, the cosmetic result was favourable in 83.78% (31/37). None of these patients had a corrective surgery such as reduction mammaplasty or mastopexy. Mean weight of excised tissue was 215 g. The 5-year local recurrence rate was 10.8%. The 5-year metastasis-free survival rate was 81.1%. The 5-year overall survival rate was 86.5%. CONCLUSIONS: Surgical treatment of multifocal and T2 breast cancers larger than 3 cm in diameter situated in the upper outer quadrant and performed with "V"-technique gives a good aesthetic result and enables a wide resection of breast tissue around the tumour

Prevalence of anencephaly in the region of Rijeka, Croatia.

This retrospective study determines the prevalence of anencephaly in the region of Rijeka, Croatia. Records of all spontaneous and therapeutic abortions terminated in medical institutions, all fetuses weighing more than 500 g or more than 22 weeks gestation (whether the product of abortion, therapeutic termination, stillborn or liveborn) and infants who died in the first year of life in the region of Rijeka, Croatia, during the 1963-2000 period were reviewed. There were 135,451 births; 22 of them were anencephalics (19 stillborn), which comprises 0.2% of all births and 2.1% of stillbirths. Annual prevalence of anencephaly varied in range from 0.00 to 7.42 per 10,000 births. In two cases pregnancy was electively terminated after ultrasonographic diagnosis of anencephaly. Fifteen anencephalics were female, six were male, and in one case sex was undetermined due to aplasia of genital organs. Associated congenital malformations were detected in 18 anencephalics. The importance of establishing national and international registers of congenital malformations in all countries is stressed. The authors suggested that the setting of obligatory reporting of all congenital malformations would be the first step toward this practice in Croatia, as well as in other developing countries.

Comparison of microvessel density with tumor associated macrophages in invasive breast carcinoma.

Neovascularization, the growth and formation of capillary blood vessels, is an essential component of solid tumor growth and a critical step in metastasis. Tumor associated macrophages (TAMs) have several functions related to tumor biology including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define the TAM and microvessel density (MD) in human invasive breast carcinoma NOS and to correlate their values with lymph node status, tumor size, tumor grade and mitotic activity index (MAI), and, finally, to determine whether MD is connected with TAMs. A total number of 57 invasive breast carcinomas NOS were processed for immunohistochemical analysis using mAb to F-VIII to visualize endothelial cells and mAb to CD68 antigens for macrophages. Statistical analysis showed only a positive correlation between TAMs and MAI (p = 0.004). These results support the notion that intensity of tumor angiogenesis does not provide additional prognostic significance, while TAMs may play a positive role in breast cancer micro system since they regulate tumor proliferation.

The lectin-binding sites for peanut agglutinin in invasive breast ductal carcinomas and their metastasis.

Peanut agglutinin (PNA) lectin-binding site patterns in primary invasive breast ductal not otherwise specified (NOS) carcinomas are related to aggressiveness of the tumor. The present study was designed to compare the expression of PNA-binding sites in the primary tumor and in local lymph node metastases. The expression of lectin-binding sites was studied using the avidin-biotin complex/immunoperoxidase technique and analyzed in relation to age of the patient and size of the breast cancer. Breast cancers and their metastases showed negativity or positivity, the latter being divided into "apical" and "non-apical" (i.e. membrane and/or cytoplasmic) depending on the main localization of staining in tumor cells. No correlation was found between primary tumors and metastases as regards PNA-binding patterns, which confirms the opinion that advanced primary tumors are polyclonal and that selected subclones of malignant cells give rise to metastases. Furthermore, the fact that primary tumors with PNA non-apical expression, a feature related to aggressiveness and poor differentiation, may have lymph node metastases with apical expression, suggests that this pattern, although no longer evident in the primary tumor, is involved in the process of cell metastasis.

Nuclear grade in invasive ductal breast carcinoma. Comparative study on nuclear grade and morphometric parameters, hormonal receptor status, flow cytometric analysis and lectin histochemistry.

Histologic and nuclear grading (NG) have been widely used to predict the prognosis in patients with advanced breast cancer. However, NG has been criticized as a non-standard (several grading schemes used) and subjective (significant interobserver variability) method for predicting the biologic behavior of this tumor. Our results on 106 invasive ductal breast carcinomas demonstrate that NG correlates with morphometric prognostic index (MPI) (p < 0.007) (lower value of MPI is connected with lower NG of 1-2 and better prognosis), with estrogen receptor (p < 0.0002) and progesteron receptor status (p < 0.04) (hormonal receptor positive tumors having lower NG). NG correlates with s-phase fraction (SPF), p < 0.04, values lower than 9.6% corresponding to lower NG. We consider NG to give important information about the biologic behavior of the tumors under observation, demonstrating a good correlation with more established parameters such as MPI and SPF.

The lectin-binding sites for peanut agglutinin in invasive breast ductal carcinomas and their role as a prognostic factor.

The present study was designed to analyze the expression of lectin-binding sites for peanut agglutinin (PNA) in paraffin sections of primary invasive ductal carcinoma not otherwise specified and to consider PNA lectin histochemistry as a further aid in the prognostic evaluation of breast cancer. The expression of lectin-binding sites was studied using the avidin-biotin complex/ immunoperoxidase technique, and analyzed in relation to the different clinical, pathological, and biological parameters of the primary disease, i.e. the presence or absence of nodal metastases, pre- or post-menopausal age, size of the tumor, mitotic activity index, morphometric prognostic index, DNA content, S-phase fraction, and steroid receptor status. The results show significant differences in PNA binding patterns among malignant epithelial breast cells. There was no expression of PNA-binding sites in 14 out of 157 tumors, while 64 showed mostly apical (membrane) staining and 124 non-apical (membrane and/or cytoplasmic) staining. Apical staining was mostly observed in patients without lymph node metastasis, with positive steroid receptor status, and those who were postmenopausal diagnosis; non-apical staining was mostly observed in lymph-node-positive premenopausal patients negative for steroid receptors and with aneuploid tumor cells. Our results indicate that, in malignant breast cells, there is an alteration of cell-surface glycoconjugates, shown by heterogeneity within a histopathologically defined group, which is related to different properties of tumor cells. The apical PNA binding pattern indicates a better differentiation of tumor cells while non-apical PNA binding suggests a higher metastatic potential. Specific PNA lectin binding patterns should be considered as a further reliable prognostic factor in breast cancer.

Expression of beta-1 integrins on tumor cells of invasive ductal breast carcinoma.

The integrins are transmembrane alfabeta heterodimers mediating cell-cell as well as cell-extracellular matrix interactions. The present study was designed to analyse the expression of beta-1 integrins on cryostat sections of invasive ductal carcinomas not otherwise specified by avidin-biotin complex immunoperoxidase technique, and to compare it with the morphometric prognostic index (MPI). The results show that the expression of beta-1 integrins is heterogeneous in the tumors. This heterogeneity was observed in quantitative and qualitative staining pattern. There was an absent expression of beta-1 integrins in 22 out of 55 tumors while 33 showed staining, weak on 23 cases and strong on 10 infiltrative ductal carcinomas. Statistical analysis pointed to some correlation of beta-1 integrins with some morphometric parameters. Low or absent expression of beta-1 integrins correlated significantly with tumors exceeding 2 cm (p < 0.0245). Moreover, a larger proportion of tumors with positive lymph nodes showed absence of beta-1 expression compared with negative lymph node, and this was also statistically significant (p < 0.0076). Correlation between mitotic activity index and staining intensity for beta-1 integrins was not found (p < 0.372). When tumors with different beta-1 expression were subdivided according to MPI values into two groups, one group with a low-risk, < 0.6, and second with a high risk, > 0.6, concordance in prognostic value was shown between MPI and beta-1 expression (p < 0.0193). These results support the idea that loss of beta-1 integrins correlates with the invasive and metastatic potential of tumor cells.