Michał Jeleń

Androgen receptors as a prognostic and predictive factor in breast cancer.

Many theoretical and experimental models indicate that androgen receptors can play an important role as prognostic factors in breast cancer. The aim of this study was to evaluate the correlations between the presence of androgen receptors on cancer cells and other selected prognostic and predictive factors with established clinical significance in women with breast cancer after radical surgical treatment. 488 adult females were included in the study, who underwent primary radical surgery for breast cancer. 428 patients (87.7%) had Pateys conservative radical mastectomy and 60 (12.3%) Halsteds radical mastectomy. The mean age at operation was 54.3, ranging from 32 to 79. The mean length of hospitalization was 7.2 days for the patients after Pateys mastectomy and 9.8 days for those after Halsteds mastectomy. The androgen receptor is the most frequently detected steroid receptor on breast cancer cells. Therapeutic efficacy of adjuvant hormone therapy was higher in the group of androgen receptor-positive patients than in androgen receptor-negative ones. The prognosis for androgen receptor-positive patients who underwent adjuvant hormone therapy was better than for those androgen receptor-positive patients who did not receive hormone therapy after primary radical surgery for breast cancer. Assessment of androgen receptor levels on cancer cells should become a routine procedure with patients undergoing primary radical surgery for breast cancer, as it seems to be an important predictive factor.

Expression of c-myc oncoprotein in laryngeal squamous cell carcinoma.

Objective c-myc seems to play a pivotal role in normal growth and development as well in cellular transformation and carcinogenesis. Overexpression of the c-myc oncogene has been observed in many hematopoetic and solid tumors. The role of c-myc protein in squamous cell carcinoma of the head and neck in general and laryngeal squamous cell carcinomas (LSCCs) in particular is far from clear. The aim of this study was to evaluate the relations between the level of c-myc protein in LSCCs and the clinicopathological data of patients, DNA ploidy and the SG2M phase index (PI). Material and Methods The c-myc protein level was evaluated immunohistochemically in tumor specimens from 50 patients with LSCC. The DNA index and SG2M PI were determined by means of flow cytometry. Results We found c-myc protein in 34 (68%) tumors. Expression of c-myc protein was demonstrated to be frequent in non-metastatic cases (p=0.016). There was no association between c-myc protein level and age, primary tumor size, histological grading or type of cancer. In 13 (26%) cases we observed DNA aneuploid tumors. The mean value of the SG2M PI was 22.5%. Expression of c-myc protein was not related to SG2M PI or DNA ploidy. Conclusions We have shown that c-myc oncoprotein may be involved in the genesis of LSCC. Our findings suggest that the detectability of c-myc protein is associated with a lower metastatic potential. The c-myc oncogene is probably not as important in laryngeal cancers compared to other cancers. Further investigations must be performed to establish the value of predicting nodal metastases in LSCC.

Expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in laryngeal squamous cell carcinomas

Matrix metalloproteinases (MMPs) that have a proteolytic activity against the components of extracellular matrix (ECM) play an important role in the invasive and metastatic spread of tumors. The role of MMPs and tissue inhibitors of MMPs (TIMPs) in laryngeal squamous cell carcinoma (LSCC) has not been elucidated sufficiently. The aim of the present study was to evaluate the correlation between the expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and TIMP-1, as well as the clinicopathological features of LSCCs. The expression of collagenases and TIMP-1 was examined immunohistochemically in 50 cases of surgically obtained specimens of primary LSCCs. Analyses indicated that LSCC cells as well as stromal cells expressed MMP-1, MMP-13 and TIMP-1 immunostaining. Overexpression of TIMP-1 occurred more frequently in non-metastasizing cases ( P =0.009). TIMP-1 and MMP-1 staining correlated significantly with the histologic type of LSCC. The keratinizing type of carcinomas exhibited higher TIMP-1 protein expression than the nonkeratinizing variety ( P =0.01). TIMP-1 staining was associated with the grade of differentiation, since it was found predominantly in well and moderately differentiated carcinomas ( P =0.04). The findings confirm that expression of analyzed MMPs and TIMP-1 is characteristic of LSCC and that these enzymes contribute to the progression of tumors. TIMP-1 upregulation might exhibit lower metastatic potential in LSCCs and is linked rather with an early stage of tumor progression. It seems also that TIMP-1 expression is dependent on the grade of differentiation.

Molecular markers [c-erbB-2, p53] in breast cancer

The aim of our study was to evaluate the correlation between clinical characteristics, histopatologic features and c-erbB-2 as well as p53 expression in cancer tissues. Breast cancer tissue was obtained from 184 female subjects with primary breast cancer. According to hormonal status patients were divided into two groups - 64 belonged to the premenopausal group and 120 to postmenopausal group. Each patient underwent mammectomy and axillary lymphadenectomy. c-erbB-2 protooncogene was detected in 54% cases, and was correlated with infiltrating type of cancer growth, as well as larger tumor size. The presence of p53 antioncogene was observed only in 33% of cases, mainly in infiltrating duct carcinomas. The incidence of c-erbB-2 and p53 positive cases was higher among subjects, whose ultrasound and mammography revealed malignancy. There was no correlation found between of c-erbB-2 expression and axillary lymph nodes involvement It seems probable, that c-erbB-2 and p53 status of cancer tissue may prove to be useful in assessment of the level of biological aggressiveness in breast carcinomas and hence can be used as a prognostic factor.

Decreased Expression of CXCR4 Chemokine Receptor in Bone Marrow after Chemotherapy in Patients with Non-Hodgkin Lymphomas Is a Good Prognostic Factor

Background CXCR4 chemokine receptor is constitutively expressed on normal and malignant B lymphocytes derived from patients with B-cell lymphoproliferative disorders and has a significant role in cell migration to lymph nodes and bone marrow. Non-Hodgkins lymphomas (NHL) constitute a heterogeneous group of lymphoproliferative diseases, which can localize not only to lymph nodes, but also can migrate to peripheral blood and metastase to other organs, including bone marrow. Aim The purpose of this study was to determine CXCR4 gene expression in peripheral blood and bone marrow of NHL patients before and after treatment. Methods Samples of lymphoma lymph nodes, peripheral blood and bone marrow aspirates of patients with B-cell NHL were taken at diagnosis and after chemotherapy. Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Expression was estimated from 0 AU (no amplificate signal) to 3 AU (maximal amplificate signal). Results No significant difference in the level of CXCR4 expression was found in reactive lymph nodes compared to lymphoma samples We observed high level of CXCR4 expression in most patients before treatment: in bone marrow: 3 AU-10 pts, 2 AU–8 pts, 1 AU–2 pts. In peripheral blood: 3 AU–14 pts, 2 AU–4 pts, 1 AU–1 pts, 0 AU–1 pts. After chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow: 3 AU–5 pts, 2 AU–7 pts, 1 AU–5 pts, 0 AU–3 pts (p = 0.03). Peripheral blood: 3 AU–2 pts, 2 AU–6 pts, 1 AU–10 pts, 0 AU–2 pts (p = 0.0002). There was a good response to treatment in patients with significant decrease of CXCR4 expression in the bone marrow after treatment with 10-fold lower risk of death (p = 0.03). Conclusions Decrease in CXCR4 expression in the bone marrow of NHL patients after chemotherapy may be a good prognostic factor.

The importance of preoperative elevated serum levels of CEA and CA15-3 in patients with breast cancer in predicting its histological type

It is not known whether in patients with breast cancer the occurrence of elevated serum tumour markers depends on its histological type. The aim of the study was to assess relationship between breast cancer histological type and the presence of increased serum levels of CEA and CA 15-3. The study population was 428 patients (all women, mean age 52.5 years), treated at The Department of Surgery of Wroclaw Medical University from 2005 to 2008 due to breast cancer. All of them had their preoperative CA 15-3 and CEA serum concentrations measured. According to the TNM system, 21% of patients were in stage I, 32.5% in stage II, 46.5% in stage III of the disease. In patients with ductal type of the cancer the elevated serum levels of CEA and CA 15-3 were observed in 48.7% and 42.2%, in lobular type in 42.4% and 52.5%, and in non-ductal/tubular types in 48.1% and 40.4% (p=N/S). Stepwise logistic regression analyses showed that ductal breast cancer is related to elevated CEA and normal CA 15-3 serum levels. The histological types of breast cancer are not significantly related to elevated serum levels of CEA and/or CA 15-3.

C-erbB-2 Immunostaining in Laryngeal Cancer

Tumour progression is strongly associated with a series of specific genetic changes in protooncogenes and tumour suppressor genes. One of the potential factors involved in tumorogenesis of squamous cell carcinomas is protooncogene c-erbB-2 (also known as neu or HER2). The authors analysed the expression of c-erbB-2 oncoprotein in 154 cases of laryngeal squamous cell carcinomas and its relationship to the clinical outcome of the patients. The difference in c-erbB-2 oncoprotein expression between the control group and cancer patients was on the statistical borderline (p = 0.0470). There was no significant correlation between c-erbB-2 expression and sex and age of the patients. T stage, lymph node status, site and histopathological grading of the tumour and clinical outcome of the patients. Univariate analysis revealed no correlation between c-erbB-2 expression and survival rates. We conclude that immunohistological examination of c-erbB-2 on paraffin section is not a valuable prognostic factor in laryngeal carcinoma.

Bronchial hyper-responsiveness, subepithelial fibrosis, and transforming growth factor-β1 expression in patients with long-standing and recently diagnosed asthma

Introduction:Chronic inflammation in asthmatic airways leads to bronchial hyper-responsiveness (BHR) and the development of structural changes. Important features of remodeling include the formation of subepithelial fibrosis due to increased collagen deposition in the reticular basement membrane. Transforming growth factor (TGF)-β might be a central mediator of tissue fibrosis and remodeling.Materials and Methods:Immunohistochemistry was used to measure collagen III deposition and TGF-β1 expression in biopsies from patients with long-standing asthma treated with inhaled corticosteroids, patients with recently diagnosed asthma, and control subjects. Computer-assisted image analysis was used to evaluate total basement membrane (TBM) thickness.Results:Asthmatics, particularly those with long-standing asthma, had thicker TBMs than healthy subjects. Collagen III deposition was comparable in the studied groups. BHR was not correlated with features of mucosal inflammation and was lower in steroid-treated patients with long-standing asthma than in subjects with newly diagnosed asthma untreated with steroids. Epithelial TGF-β1 expression negatively correlated with collagen III deposition and TBM thickness.Conclusions:The study showed that TBM thickness, but not collagen III deposition, could be a differentiating marker of asthmatics of different disease duration and treatment. The lack of correlation between BHR and features of mucosal inflammation suggests the complexity of BHR development. Corticosteroids can reduce BHR in asthmatics, but it seems to be less effective in reducing subepithelial fibrosis. The role of epithelial TGF-β1 needs to be further investigated since the possibility that it plays a protective and anti-inflammatory role in asthmatic airways cannot be excluded.

Massage-induced morphological changes of dense connective tissue in rat’s tendon

The aim of the experiment was to determine if possible changes in connective tissue induced by massage could have a positive effect justifing the use of massage in all post-traumatic connective tissue conditions, e.g. tendon injuries. The investigations were performed in a group of 18 Buffalo rats. The rats were divided into two groups (experimental and control). To standardize the massage procedure, it was performed with an algometer probe of 0.5 cm2 with constant pressure force of 1 kG (9,81 N). To analyse the number and diameter of collagen fibrils, two electron micrographs were performed for each rat of the collected segments of tendons of rat tail lateral extensor muscle. After image digitalization and calibration, the measurements were carried out using iTEM 5.0 software. The number of fibrils, their diameter and area were measured in a cross-sectional area. An increase of the number of collagen fibrils was observed in the tendons of massaged animals compared to the control group. Our study demonstrated that massage may cause a beneficial effect on metabolic activity of tendons fibroblasts and, in consequence, may be applied for more effective use of massage for the prevention of tendon injury as well as after the injury has occurred. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 103-106).

Prognostic value of CA 19-9 level in resectable pancreatic adenocarcinoma

The prognosis in patients with pancreatic cancer is poor and some authors describe it as a lethal disease. At the time of diagnosis only 14% of patients could be surgically treated and up to 30% of them die within 12 months. Therefore, further clinical investigations on preoperative patient qualification are needed. A total of 81 patients were included into the study. The CA 19-9 concentration was measured before surgery by an automated, commercially available enzyme immunoassay in Axsym analyzer (Abott Diagnostics Laboratory). A value of 37 U/ml was used as the upper limit of normal levels. Tumors were staged according to the Union Against Cancer (UICC) of 2004 and graded during the histological evaluation according to the G0-G4 scale. All patients were monitored every three month via outpatient clinic visits. In the case of missing visit we contacted the families to establish the cause. We assessed perioperative, 12 month, 2 year and 5 year survival. Twelve moth, 2 year and 5 year survival were assessed in the whole studied population and in the group of patients with the exception of these who died during the perioperative period. The total five year survival was 6%. The median time of survival was 467 days (range: 163 - 586 days). The perioperative period was survived by 91.4% patients, 12 months were survived by 71.6% patients, 2 years were survived by 35.8% patients, 5 years were survived by 6.2% patients. The serum Ca 19-9 level was above the normal limit in 80.5% patients. ROC curve analysis revealed that CA 19-9 level of more than 106 U/ml was linked to 2 year survival with 79.3% sensitivity and 74.5% specificity. Preoperative level of CA 19-9 below 106U/ml represents a predictive factor of 2- and 5-year survival, independent of other factors, such as lower size of the tumor, absence of metastases to lymph nodes, female gender of patients. After exclusion of the patients who died in the perioperative period, no relationship could have been disclosed between preoperative CA 19-9 levels and one year survival. The observation points to the chance that patients with higher levels of CA 19-9 harbour micrometastases, the development of which is sufficiently slow to allow for a one-year survival of the patients but which increase the risk of death after two and five years.