Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients.

Survivin, encoded by BIRC5 gene (baculoviral IAP repeat containing 5), belongs to the family of inhibitors of apoptosis proteins (IAPs). In mammalian cells it participates in the control of mitosis, apoptosis regulation, and cellular stress response. Its expression is increased in almost all types of cancers. The aim of this study was to investigate the role of BIRC5 polymorphisms in breast cancer (BC) and to connect survivin expression with various clinicopathological characteristics of BC patients. Blood and archival tumour tissue samples were collected from 26 BC patients from Croatia. Survivin expression was determined immunohistochemically. BIRC5 promoter, coding region, and 3'UTR were genotyped. DNA from 74 healthy women was used as control. BIRC5 polymorphisms and survivin expression were tested against age of onset, histological grade, tumour type and size, lymph node status, oestrogen, progesterone, Her2, and Ki67 status. Numbers of samples with weak, moderate, and strong survivin expression were 9 (33.3%), 11 (40.7%), and 7 (25.9%), respectively. Most patients had nuclear survivin staining (92.6%). High survivin expression was significantly associated with negative oestrogen receptor status (p=0.007) and positive Ki67 expression (p=0.032). Ki67 expression was also positively correlated with histological grade (p=0.0009). Fourteen polymorphisms were found in BC samples, located mostly in promoter and 3'UTR of BIRC5. There was no significant difference in the distribution of polymorphisms between BC and control samples. Among clinicopathological characteristics of BC patients, alleles of five BIRC5 polymorphisms were associated with younger age of onset: c.-644T>C (55.8 years [y] vs. 48.1 y; p=0.006), c.-241C>T (54.2 y vs. 45.0; p=0.029), c.9809T>C (55.8 y vs. 48.1 y; p=0.006), c.-1547C>T (58.3 y vs. 50.9 y; p=0.011), and c.9386T>C (50.8 y vs. 59.5 y; p=0.004). To assess the significance of BIRC5 polymorphisms and survivin expression as predictive and prognostic biomarkers for BC further research with a larger sample size is needed.

IMMUNOHISTOCHEMICAL DIFFERENTIATION OF TRIPLE NEGATIVE BREAST CANCER.

Based on immunohistochemical staining for the basal markers cytokeratin 5/6 (CK 5/6), cytokeratin 14 (CK 14) and P-cadherin, triple negative tumors (TNT) are divided into two groups: 1) basal-like (BL) positive for one or all three markers; and 2) non basal-like (NBL) negative for all three markers. Even though the different origin of the cells of these two types of tumors implies different biological properties, they had been treated as one entity until recently. This paper analyzes TNT collected from 150 patients and distributed into two groups according to the results of immunohistochemical analysis, i.e. BL 116 (77.3%) and NBL 34 (22.67%). In this study, CK 5/6, CK 14 and P-cadherin were used as markers for identifying BL tumors. The immunohistochemical reaction was positive for CK 5/6 in 37%, for CK 14 in 50.86% and for P-cadherin in 68.34% of cases. The subclassification of triple negative breast cancer using the basal markers CK 5/6, CK 14 and P-cadherin has enabled identification of BL and NBL breast cancers in a proportion that is in line with the only accurate analysis of TNT gene expression. Using the mentioned combination of markers in daily practice is easy to perform and economically affordable.

Case report of nodular melanoma within congenital melanocytic nevus- primary closure challenge.

INTRODUCTION: Congenital melanocytic nevi (CMN) are present in 1-2% of newborn infants. The size of CMN defines the risk of developing melanoma which is estimated from 5-10%, especially in lesions that are located across the spine. PRESENTATION OF CASE: Herein we report a case where nodular melanoma was discovered on the periphery of medium sized CMN in a high risk patient. After complete excision, the defect was reconstructed with random pattern, triple rhomboid flap. DISCUSSION: Melanoma that arose within medium sized CMN would leave a complex posterior lower trunk defect. We used a triple Limberg flap which was proven to be straightforward and simple method when large defects are to be covered with vital tissue. We have also showed that this type of reconstruction is suitable for high risk patients that could not withstand any complex procedures. CONCLUSION: In our case, the method we choose to reconstruct the defect proved to be simple, safe and easy, especially when surgery is performed in a high risk patient.

Expression of genes responsible for the repair of mispaired bases of the DNA (MLH1) in invasive ductal breast carcinoma.

Breast cancer is a heterogeneous group of diseases determined and distinguished by cellular type, gene expression and clinical signs and symptoms. Identification of histological and biological markers is of great value in predicting the progression of tumor growth and anticipating the expected response to various treatment options. Due to a high degree of cell proliferation in breast tumors and high genetic instability of these tumors, as a consequence of defective DNA repair mechanisms, chemotherapy as a treatment option often renders very successful results. During our scientific research we wanted to determine the involvement of the genetic polymorphisms of DNA mismatch repair system (MLH1 gene) and the subsequent development of breast carcinoma. This study included 108 patients who were surgically treated for invasive breast cancer at the Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital "Dubrava". The expression of the MLH1 gene was determined by immunohistochemical methods. The results showed that 82.9% of tumor cells expressed the MLH1 gene. Analysis of survival rate for patients with invasive ductal breast cancer showed a statistically significant (p = 0.043) correlation with the expression of MLH1 genes. The overall five year survival rate of our patients was 78.7%. These results indicate that there is a possible involvement of MLH1 gene in the progression and development of breast cancer.

Influence of hormonal status on thermography findings in breast cancer.

The aim of this study was to investigate the association of infrared imaging findings and hormone receptor (estrogen and progesterone) status in breast cancers. The study was carried out at Department of Surgical Oncology and Department of Pathology, Sestre milosrdnice University Hospital Center, in collaboration with licensed infrared thermography experts. The study involved 75 female patients with invasive breast tumors. Thermography findings were compared with different immunohistochemical findings (hormone status positive or negative). Seventy-five female patients aged 36 to 86 years, mean age 64 +/- 11.36 years, were examined. The tumor itself and the breast containing the tumor were statistically significantly warmer (p < 0.001) than the healthy breast in all study patients. There was no statistically significant difference (p > 0.05) between patients with positive and those with negative estrogen receptors. Unlike all previously published results of various thermographic studies, results obtained in this study on the hormone receptor status analyzed and its impact on thermographic findings indicated that estrogen negative tumors had a higher maximum and average temperature than estrogen positive tumors. It was also observed that estrogen negative tumors had lower impact on warming of the entire breast, and that maximum and average temperature of the affected breast was higher in estrogen positive tumors. Arithmetic means of maximum and average tumor temperatures were statistically significantly higher for progesterone negative tumors compared with progesterone positive tumors (p < 0.05). Thermographic findings correlated with the specific hormonal status of breast invasive tumors, which reflects the biological behavior of tumors as well as their clinical variables.

The impact of human epidermal growth factor receptor-2 status of invasive breast tumors on thermography findings.

OBJECTIVE: To analyze the impact of prognostic human epidermal growth factor receptor-2 (HER-2) in invasive breast cancers on the findings of thermography tests. METHODS: The study was carried out at the Department of Surgical Oncology and the Department of Pathology, University Clinical Hospital Center, Sisters of Mercy, Zagreb, Croatia, in collaboration with licensed infrared (IR) thermography experts. The study involved 75 female patients diagnosed with invasive breast cancer from May to July 2011. Thermography findings were compared between different immune-histochemical (IHC) findings (HER-2 status: positive or negative). RESULTS: Significantly higher temperatures were recorded in invasive cancer breasts than in healthy breasts. The cancer sites and the entire cancer breasts were significantly warmer (p less than 0.001) than the healthy breasts and opposite tumors mirror sites. Considering the HER-2 status, HER-2 positive invasive cancers were significantly warmer in comparison with the HER-2 negative cancers (p=0.035). CONCLUSION: The trend of increased temperature in HER-2+ tumors was noted. The findings clearly indicate that HER-2+ status has a higher impact on the increased thermographic temperature findings.

Primary Ewing's sarcoma of the kidney: a case report.

Primary adult Ewing's sarcoma is a rare entity. They most commonly occur in children and young adults. 6% of them are localized extraosseously. We present a case of a 51 year old patient with primary renal Ewing's sarcoma and multiple metastases in liver and iliac bone. Patients with metastatic disease are usually treated with aggressive chemotherapy and have a poor outcome. Our patient underwent complete surgical excision of tumour, and was treated with aggressive chemotherapy, respectively. Two and half years after presentation he is well, without any symptoms.

[Epidemiology of invasive breast cancer according to histopathologic and immunohistochemistry prognostic factors]. / Epidemiologija invazivnih tumora dojke s obzirom na patohistoloske i imunohistokemijske prognosticke cimbenike.

The aim of this study was to analyze the TNM classification factors of invasive breast cancer that can be affected by the national program for early detection of breast cancer in the Republic of Croatia. The other analyzed factors related to histology and immunohistochemistry have no such impact as they are related to biological behavior and aggressiveness of malignant breast tumors, thus providing useful predictive and prognostic information. The study was performed at Department of Oncologic Surgery, Sestre milosrdnice University Hospital Center, and included 75 patients surgically treated for invasive breast cancer during the period of one month in 2011, mean age 64 +/- 11.36 (range 36-86) years. Most of the patients (68%) with malignant breast disease were diagnosed in a localized stage, which is consistent with the reports from developed European countries. The size of the newly discovered tumors showed continuation of a trend of detecting tumors of ever less size and a lower percentage of pT3 pT4 tumors. This result proved superior to those reported from many European countries. The results of correlation analysis, tumor size, estrogen and progesterone receptor, HER-2 protein, Ki-67, and histologic tumor grade, tumor size did not show significant correlation with any of these parameters. Concordant expression of phenotype (ER+, PR+) receptor pairs and negative HER-2 was recorded in most study patients. The second most frequent group had tumors with so-called 'triple-negative' immunohistochemistry negative phenotype (ER-, PR-, HER-2). In conclusion, the program of early detection of breast cancer in the Republic of Croatia and at the University Hospital for Tumors justifies its existence for revealing malignant breast tumors at an earlier stage of the disease considering the size local stage of newly diagnosed tumors.

Rectal metastasis from lobular carcinoma of the breast: a case report.

Rectal metastases from breast carcinomas are very rare. They often occur in lobular invasive breast carcinoma (ILC), usually after a long disease-free period. It is important to be aware of these unusual metastatic patterns of ILC of the breast because of the possibility of systemic therapy. We present a case of 83-year old woman with rectal metastesis from ILC seven years after surgery of primary tumor.

Histological types of polypoid cutaneous melanoma II.

The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type.

[Analysis of prognostic factors in breast cancer at University Hospital for Tumors]. / Analiza prognostickih cimbenika kod karcinoma dojke u Klinici za tumore.

Breast cancer is the most common malignant disease in women. It is rare before age 30, whereafter its prevalence rises to reach peak at age 50. Prognostic factors have a very important role in choosing the most appropriate treatment option and making long-term disease prognosis. Currently, the classic prognostic factors such as histologic type, tumor grade, tumor size, regional lymph node involvement, estrogen and progesterone receptor status still are of high prognostic value allowing for reliable prognosis. This retrospective study included female patients treated at Department of Surgery, University Hospital for Tumors in Zagreb over a two-year period (2002-2003). Only patients with histologically diagnosed invasive ductal breast cancer (NOS) undergoing radical modified mastectomy were included in the study. Analysis of the generally accepted prognostic parameters (tumor size, regional lymph node status, tumor grade, hormone receptor status) confirmed their known prognostic value. Study results were consistent with internationally reported data, reflecting appropriate approach by the surgery-pathology team of the hospital in the management of breast cancer.

Significance of the relative size of a breast tumor in deciding the method of surgical treatment.

AIM: In the surgical treatment of breast cancer there are basically two options: radical and breast-sparing surgery. The main criterion in deciding the mode of treatment is the absolute size of the primary tumor. The purpose of this study was to analyze the relative size of a breast tumor as a prognostic factor and to establish boundary values of the relative tumor size for breast-sparing or radical surgery. METHODS: The relative volume of the breast tumor was analyzed in 200 female patients treated at the Zagreb University Hospital for Tumors. All patients were diagnosed with ductal invasive carcinoma and underwent radical surgery. RESULTS: The study found the correlation between the relative volume of the tumor and tumor grade (r = 0.805, P = 0.24) and between the relative volume of the tumor and the involvement of regional lymph nodes (r = 0.493, P = 0.14). These correlations confirmed the possible prognostic value of the relative size of a breast tumor. CONCLUSIONS: Three percent is the boundary value of the relative volume of a tumor at which its biological potential changes and the pathohistological level of a tumor and the number of affected lymph nodes increases. The relative size of 3% could therefore be considered a boundary value in making a decision about the method of surgical treatment (breast-sparing or radical surgery). For tumors with a relative size of less than 3%, breast-conserving surgery is recommended for its lesser malignant potential and the possibility of performing wide extirpation (extirpation 1-2 cm from the tumor margin), regardless of the size of the breast.

[Leiomyosarcoma of the breast]. / Leiomiosarkom dojke.

A 62-year old patient was treated at our hospital for a palpable change in the upper part of the left breast. The clinical finding was preoperatively confirmed by radiologic, ultrasound and cytology studies, however, the potential biologic process (malignant/benign) was not thus verified. Considering undefined diagnostic nature of the process, biopsy, pathohistology and immunoanalysis were performed to indicate leiomyosarcoma mammae. The incision interspace at certain sites was less than two centimeters, indicating radical breast excision in toto (ablation with evacuation of the contents of the axilla). At the time of scheduled surgery, the patient sustained cardiologic discomfort, so tumorectomy was supplemented by locoregional radiotherapy. Leiomyosarcoma of the breast is a very rare primary malignant breast tumor, with only 14 cases reported in the literature. Considering the rare occurrence of leiomyosarcoma of the breast, in radical surgery we used attitudes like in other breast tumors and leiomyosarcoma of other localizations.

Radiotherapy of stage IEA primary breast lymphoma: case report.

A 47-year-old woman was referred for the treatment to our Hospital because of a palpable nodule in the upper medial quadrant of her right breast. After tumor excision, pathohistological examination showed a follicular center cell lymphoma grade 2, B-cell type (CD20+, bc16+, CD10+, bcl2+). The final diagnosis was stage IEA primary extranodal non-Hodgkin s breast lymphoma. The involved breast was irradiated isocentrically with two opposite 6-megavolt (MeV) photon beams delivered from the linear accelerator (tangential fields) using asymmetric collimator opening. Radiation volume, inclinations of the medial and lateral field, and the part of the underlying chest wall and lung parenchyma were determined during the radiotherapy simulation process. The total irradiation dose was 44 Gy delivered in single daily doses of 2 Grays (Gy). After breast photon irradiation, a boost to the tumor bed was performed by a direct 12 MeV electron beam, with a total dose of 6 Gy delivered over three days. Since primary non-Hodgkin lymphoma of the breast is rather rare, there has been no uniform approach to its treatment. The advantage of applying the asymmetric collimator jaw opening in breast radiotherapy is the instant reduction of the dose at margin fields, resulting in both the protection of neighboring lung parenchyma and the good coverage of planned target volume.

Rare complication of breast cancer irradiation: postirradiation osteosarcoma.

Radiation-induced osteosarcoma is a rare complication of radiation therapy for breast cancer. The authors present a 60-year-old patient in whom osteosarcoma of the chest wall developed 5 years after modified radical mastectomy and radiation therapy for breast cancer. One year after resection of the chest osteosarcoma, metastasis to the contralateral axillary lymph nodes developed and these were removed. Radiation-induced osteosarcoma is difficult to treat and has a poor prognosis, thus early diagnosis is necessary for optimal treatment.