Correlation between PARP-1 immunoreactivity and cytomorphological features of parthanatos, a specific cellular death in breast cancer cells.

In parthanatos, a PARP-1 (poly (ADP-ribose) polymerase 1)-mediated cell death, dissipation of mitochondrial membrane potential, large-scale DNA fragmentation and chromatin condensation were observed. In contrast to apoptosis, it does not cause apoptotic bodies formation. Although PARP-1-mediated cell death presents loss of membrane integrity similar to necrosis, it does not induce cell swelling. The purpose of the study was to correlate the immunohistochemical parameters of PARP-1 reactivity and the selected cytomorphological features of parthanatos: the lack of apoptotic bodies and the absence of necrosis in breast cancer (BC) specimens. Immunohistochemistry for PARP-1 was performed on 83 BC specimens. Correlations between parameters of PARP-1 expression and sub-cellular localisation and the presence of apoptotic bodies and necrosis were evaluated. High expression of PARP-1 (ImmunoReactive Score ≥6) was associated with the lack of apoptotic bodies (P=0.013) and with the absence of necrosis (P=0.002). The presence of apoptotic bodies was correlated with re-distribution of PARP-1 from the nucleus to cytoplasm in BC cells (P=0.029). Additionally, a tendency was observed between necrosis and loss of nuclear PARP-1 expression (P=0.049). Our study suggests that PARP-1 may play a crucial role in induction and regulation of specific type of cellular death called parthanatos.

The role of surgery in the treatment of colorectal metastases from primary skin melanoma.

AIM: The study assessed the role of colorectal surgery in the treatment of metastatic melanoma and identified patients who can most benefit from surgical resection. METHOD: A retrospective analysis was made of 34 consecutive patients with skin melanoma who underwent surgical resection of large bowel metastasis. RESULTS: The median disease-free interval between diagnosis of the primary and metastatic melanoma was 24 (7-98) months. Nine (27%) patients underwent emergency surgery for obstruction and 25 (73%) had an elective procedure. Resection with curative intent was performed in 14 (41%) and palliative resection in 20 (59%) patients. There was no postoperative mortality and morbidity occurred in 9%. The median survival following surgery was 11.5 (4-68) months. The 1-, 2- and 5-year survival rates were 50%, 32% and 17% respectively. Median survival was significantly increased in patients without extra-abdominal metastases, with no evidence of non-large-bowel metastases, if the disease-free interval was longer than 24 months and when curative resection was performed. In multivariate analysis, an apparently complete or palliative resection and the absence or presence of extra-abdominal metastases were the most important prognostic factors. CONCLUSION: An aggressive surgical approach to large bowel metastatic melanoma results in good palliation and effective relief of symptoms with acceptable morbidity and mortality.

Pain experienced by patients during minimal-invasive ultrasound-guided breast biopsy: vacuum-assisted vs core-needle procedure.

AIMS: To evaluate comparatively the pain associated with ultrasound-guided core-needle (CN) and vacuum-assisted (VA) biopsy for non-palpable breast lesions. METHODS: 723 women undergoing ultrasound-guided breast biopsy for BIRADS IV and V lesions according to the same standardised protocol were prospectively studied. 14-gauge CN biopsy with an automated gun was performed in 321 patients. In 402 women biopsy was made using 11-gauge VA hand-held probe. Immediately after the procedure patients were interviewed about the pain experienced during the biopsy and were asked to indicate at the pain intensity on a eleven-point scale: from 0 (none) to 10 (extreme, worst possible pain). RESULTS: The median rate of pain experienced by women during biopsy was 4 (range 2-7). There were no significant differences between CN and VA groups with regard to age, body mass index, menopausal status, history of parity, hormone replacement therapy, menopausal status, breast parenchymal pattern (according to Wolfe's classification), family history of breast cancer, lesion size and number of samples. CN biopsy with an automated gun was significantly more painful (P < 0.01) than procedure with VA hand-held device as evaluated by patients: median 6 (4-7) vs 3 (2-5), respectively. CONCLUSIONS: Despite using the larger needle VA procedure results in less pain experienced by women in comparison to CN biopsy with automated gun. Reduced patient discomfort should be one of the reasons for the preferential use of VA biopsy in the assessment of non-palpable breast masses.

The impact of pre- or postoperative radiochemotherapy on complication following anterior resection with en bloc excision of female genitalia for T4 rectal cancer.

OBJECTIVE: The aim of the study was to assess the mortality and morbidity following extended anterior resection with excision of internal female genitalia combined with pre- or postoperative chemoradiotherapy in women with extensive rectal cancer. METHOD: The study included a consecutive series of 21 women with T4 adenocarcinoma of the rectum infiltrating the reproductive organs treated with curative intent between 1997 and 2003. All patients had an extended anterior sphincter preserving resection of the rectum (total mesorectal excision) and hysterectomy with or without posterior vaginal wall excision. In all patients, surgery was combined with adjuvant radiochemotherapy. Ten patients received preoperative radiotherapy (50.4 Gy) concurrently with two courses of chemotherapy [fluorouracil with folinic acid (FA)] followed by surgery within 6-8 weeks and subsequently four courses of postoperative chemotherapy. Eleven received postoperative chemoradiotherapy (50.4 Gy plus fluorouracil with FA). RESULTS: There was no postoperative mortality. Postoperative complications were observed in 57% patients (early in 14% and late in 52%). These included: anterior resection syndrome with anorectal dysfunction in 52% (requiring proximal diversion in 5%), urinary complications in 24% (complete incontinence requiring a permanent catheter in 5%). In addition, postoperative acute bleeding requiring relaparotomy, delayed wound healing caused by superficial infection, anastomotic leakage, prolonged bowel paralysis, benign rectovaginal fistula and anastomotic stricture occurred (5% each). The risk of postoperative morbidity (52%) was similar for patients with or without preoperative radiochemotherapy. CONCLUSION: Despite this aggressive therapeutic approach, most postoperative complications were transient or could be treated. Preoperative radiochemotherapy did not increase the risk of morbidity.

Breast cancer expression of E-cadherin does not differ between patients with positive and negative oncological history.

PURPOSE: The question of whether or not non-sporadic breast malignancies have different immunohistochemical features than sporadic malignancies has not been investigated previously. Consequently, the purpose of this study was to compare the expression of E-cadherin (EC) in breast cancer patients with positive and negative oncologic histories. MATERIAL AND METHODS: The study included 98 breast cancer patients divided into two groups: 1) without the personal or familial history of previous malignancies, and 2) with the personal history of previous malignancies and/or with the data on cancer episodes in first- and/or second-degree relatives. RESULTS: There were no significant differences in the expression of EC between breast malignancies of the two groups. Moreover, statistical relationships were not observed between the positive or negative oncologic history, the age, and the menopausal status of patients, or histological tumor grade. CONCLUSIONS: Although the results of our series revealed no significant differences in the expression of EC between assumed sporadic and assumed non-sporadic malignancies, there is a need for further comparative studies on the immunohistochemistry of both the breast carcinoma types in order to find the other biological markers that could suggest or exclude cancer susceptibility in a given patient. Nevertheless, the results of our study suggest that EC immunohistochemistry cannot be used as a surrogate marker for screening for hereditary breast cancer.

Predictive value of lymphocytic infiltration and character of invasive margin following total mesorectal excision with sphincter preservation for the high-risk carcinoma of the rectum.

PURPOSE: To assess the prognostic significance of clinicopathological factors, especially histological parameters of new Jass classification, following sphincter-sparing total mesorectal excision (TME) for high-risk rectal cancer. MATERIAL AND METHODS: Forty-five consecutive patients treated with curative intent in 1998-1999 due to rectal cancer in Dukes stage B and C were studied prospectively. All of them underwent anterior resection with TME technique. Prognostic value was evaluated by the impact on five-year recurrence-free survival (RFS) in uni- and multivariate analysis. Only factors significant in univariate analysis entered the multivariate regression model. P value <0.05 was stated as a significance limit. RESULTS: Regarding traditional clinico-pathological factors patient age, tumor site, differentiation grade, mucinous histology and the extent of direct tumor penetration did not significantly affect survival rates. Only the lymph nodes status was associated with prognosis with statistical importance (negative vs positive, RFS: 53.8 +/- 10.0% vs 26.3 +/- 10.4%, respectively). Considering the additional parameters of Jass classification the character of invasive margin of the tumor did not reveal the important predictive value although the lymphocytic tumor infiltration was significantly related to patient outcome (presence vs absence, RFS: 63.6 +/- 15.2% vs 37.5 +/- 8.7%, respectively). In multivariate analysis the only one statistically important and independent predictive parameter was the lymph nodes status. CONCLUSIONS: Lymph nodes metastases remain the most important prognostic factor after anterior resection with TME for Dukes B and C rectal cancer. From variables included into Jass classification the absence of lymphocytic infiltration of the tumor can be helpful to identify patients with enhanced risk of oncological relapse.

Multivariate analysis of oestrogen receptor alpha, pS2, metallothionein and CD24 expression in invasive breast cancers.

Determination of oestrogen receptor alpha (ER) represents at present the most important predictive factor in breast cancers. Data of ours and of other authors suggest that promising predictive/prognostic factors may also include pS2, metallothionein (MT) and CD24. Present study aimed at determining prognostic and predictive value of immunohistochemical determination of ER, pS2, MT, and CD24 expression in sections originating from 104 patients with breast cancer. An univariate and multivariate analysis was performed. Both univariate and multivariate analyses demonstrated that cytoplasmic-membranous expression of CD24 (CD24c-m) represents a strong unfavourable prognostic factor in the entire group and in most of the subgroups of patients. In several subgroups of the patients also a prognostic value was demonstrated of elevated expression of pS2 and of membranous expression of CD24. Our studies demonstrated that all patients with good prognostic factors (higher ER and pS2 expressions, lower MT expression, CD24c-m negativity) survived total period of observation (103 months). The study documented that cytoplasmic-membranous expression of CD24 represented an extremely strong unfavourable prognostic factor in breast cancer. Examination of the entire panel of the studied proteins permitted to select a group of patients of an exceptionally good prognosis.

Elevated metallothionein (MT) expression in invasive ductal breast cancers predicts tamoxifen resistance.

Elevated expression of the low molecular weight metallothionein (MT) proteins can be found typically in breast cancer cases with less favourable prognosis. The MT gene has been described to be potentially down-regulated by estrogen receptor alpha. The present study is aimed at examining the predictive value of MT expression for results of tamoxifen treatment in breast cancer in relation to steroid receptor status. Sixty patients with primary invasive ductal breast cancers with post-operative tamoxifen treatment were enrolled in the study. In paraffin sections of the studied tumours immmunohistochemical reactions were performed using antibodies directed against MT, estrogen receptors (ER) and progesterone receptors (PgR). Results of the immunohistochemical reactions and of clinical observations were analysed using multivariate progression analysis based on the Cox proportional hazard model. Elevated MT expression was demonstrated to be typical for cases with documented relapse of the disease (P<0.001) or terminated by death (P=0.03). Decreased ER expression was found to be typical for cases of a higher grade (P=0.02) and cases terminated by death (P=0.006). The multivariate analysis showed that elevated MT expression was characteristic for cases with shorter overall survival time (P=0.04). The data showed that MT carried an independent, and also independent from ER status, unfavourable predictive value as far as results of tamoxifen treatment were concerned.

Immunocytochemical evaluation of metallothionein (MT) expression in myoepithelial cells of ductal mammary carcinoma and its relation to survival time: analysis of 7-year course of the disease.

Myoepithelial cells participate in the development of mammary glands and have been suggested to play a role in the biology of mammary cancer. Recent studies demonstrated in the cells expression and overexpression of metallothionein (MT): a low molecular weight, cystein-rich protein which participates, i.a., in the multidrug resistance to cvtostatic drugs. The present study was aimed at examining the relation between results of immunocytochemical (ICC) detection of MT expression in myoepithelial cells, present in structures of a ductal mammary carcinoma, and survival of the patients. In sections originating from 43 patients with ductal mammary carcinoma ICC reactions were performed to detect MT and to confirm the presence of myoepithelial cells (using antibodies to smooth muscle actin). Survival of the patients was also determined in the course of 7-year observations. Statistical analysis using the Coxe's model did not detect relations between MT expression intensity, in the myoepithelium on one hand and patient survival on the other (chi2=0.003 p=0.96).

Analysis of estrogen receptor (ER) and estrogen-dependent pS2 protein expression in cells of mammary ductal carcinoma.

Not every case of mammary carcinoma with expression of estrogen receptors (ER) responds by remission to anti-estrogen treatment. Possible causes of the phenomenon may involve abnormalities of the receptor or defects in mechanisms of signal transmission. One of the ways in which function of the receptor may be detected involves examination of expression of the antigens which appear as a consequence of estrogen stimulation, e.g., expression of pS2 protein. The present study was aimed at comparing ER and pS2 expression in cells of mammary carcinoma, and hence, at finding out whether the presence of ER is equivalent to the sensitivity to estrogen action. In paraffin sections of ductal mammary carcinoma samples obtained from 56 patients, immunocytochemical reactions were performed using monoclonal antibodies against ER and pS2. The results documented positive correlation between the presence of ER and the presence of pS2 in cells of mammary carcinoma (Spearman's rank correlation: r=0.43, p <0.001). Thus, the intensity of pS2 expression was directly related to the expression of ER and the latter was found to be functional.

Prognostic value of immunocytochemical estimation of estrogen receptor (ER) and of pS2 estrogen-dependent protein in cells of mammary ductal carcinoma. Analysis of five-year course of the disease.

The pS2 protein belongs to the so called estrogen-dependent proteins, which appear in cells as a result of estrogen stimulation. The present study was aimed at determining prognostic value of estrogen receptor (ER) and pS2 protein expression in mammary cancer cells. The immunocytochemical reactions were performed in paraffin sections of tissue samples from 62 patients with ductal mammary carcinoma using monoclonal antibodies against ER and pS2. The analysis included also survival time of the patients, determined during the five-year observations. The studies documented a correlation between survival time and the level of ER expression (p=0.014) and absence of correlations between survival time and pS2 expression (p=0.55). The results indicate that evaluation of ER expression in mammary cancer cells may assist in defining prognosis of the patients while parallel estimation of pS2 expression in the cells is useless in this respect.