Piotr Pluta

Influence of high expression of Smac/DIABLO protein on the clinical outcome in acute myeloid leukemia patients

The role of the Smac/DIABLO protein, a novel apoptosis agonist, in acute myeloid leukemia (AML) is not clearly determined. The expression of Smac/DIABLO protein in AML leukemic cells and its relationship with clinical outcome was evaluated in this study. The intracellular expression of Smac/DIABLO protein was assessed using multi-color flow cytometry in 71 newly diagnosed AML patients treated with conventional chemotherapy. It was found that the high expression of Smac/DIABLO protein was an independent prognostic factor in terms of higher complete remission rate (p<0.001) and longer overall survival (p=0.003). Moreover the low expression of Smac/DIABLO protein was associated with poor karyotype.

Expression of IAP family proteins and its clinical importance in breast cancer patients.

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

Long-term survival of endometrioid endometrial cancer patients

Introduction To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. Material and methods A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. Results In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. Conclusions The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

The first description of sentinel node biopsy in a patient with amelanotic melanoma of the glans penis

We present the first description of sentinel node biopsy in a patient with amelanotic melanoma of the glans penis. The patient underwent partial amputation of the penis due to tumor of the glans. Pathologic examination of the postoperative specimen revealed the presence of a very rare malignancy--amelanotic melanoma. Sentinel node biopsy, with the use of the combined radiotracer/blue dye technique, was performed. Preoperative lymphoscintigraphy was performed the day before surgery. During surgery, blue dye mapping and intraoperative detection of gamma radiation were used. Two sentinel nodes were identified in the left inguinal region and one sentinel node in the right inguinal region. All sentinel nodes were an intense violet color; in each case, the level of radiation in the sentinel node was almost 20 times higher than the level of radiation in the node bed. Routine hematoxylin and eosin staining and immunohistochemistry (HMB-45) revealed the presence of micrometastasis in one of the sentinel nodes harvested from the left inguinal region. Consequently, left inguinal, iliac and obturatory lymphadenectomies were performed. The final pathologic examination revealed the presence of one metastasis (diameter, 2 mm) in one of the resected non-sentinel nodes. No relapse has been observed during 18 months of follow-up.

Significance of Bax expression in breast cancer patients.

UNLABELLED Bax protein, the proapoptotic member of Bcl-2 protein family, plays the key role in apoptosis pathway. THE AIM OF THE STUDY was to assess the expression of Bax protein in breast cancer cells. MATERIAL AND METHODS Sixty-two breast cancer patients were included in the study. The control group encompassed 11 fibroadenoma patients. Single cells were isolated from defrosted samples and prepared for flow cytometry measurement. RESULTS Median expression of Bax protein in study group was 7.9% (range: 0-49.4%) and was significantly lower than in control (median expression 15.8%; range 4.9-30.9%; p=0.034). Expression of Bax correlated with expression of p53 and caspase-3 proteins (p<0.01, rank Spearman test). In patients under 70 years old and with positive estrogen receptors status the expression of Bax protein was significantly higher (p=0.03 and p=0.01 respectively). CONCLUSIONS Lower expression of Bax protein in breast cancer cells may suggest the potential way of apoptosis avoidance of tumor cells. Correlations among Bax protein, p53 and caspase-3 are likely associated with active apoptotic mechanism in breast cancer cells expressing Bax protein. Further investigation with long time follow-up should be performed to establish the prognostic role of Bax protein expression in breast cancer patients.

Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia

The inhibitor of apoptosis protein (IAP) family acts as an inhibitor of apoptosis pathways. The potential prognostic value of the expression of selected IAP family members, XIAP, cIAP-1, cIAP-2 and survivin protein, was evaluated with regard to treatment response and survival of 56 newly diagnosed adult patients with acute myeloid leukemia (AML). The presence of these IAP members influenced the achievement of a complete response (CR). In addition, overall survival (OS) was influenced by low survivin expression in univariate and multivariate analysis (p = 0.014 and p = 0.013, respectively). A strong correlation was observed between members of the IAP family (XIAP and cIAP-1, XIAP and cIAP-2, cIAP-1 and cIAP-2, p < 0.001 for all comparisons), while Smac/DIABLO demonstrated an inverse correlation with XIAP, cIAP-1 and cIAP-2 (p < 0.001 for all comparisons). Further studies should be undertaken to better demonstrate the mode of action of IAP members, as well as their prognostic and therapeutic potentials.

TRAIL protein expression in breast cancer cells correlates with nuclear grade

Introduction TRAIL protein may serve as an escape mechanism for cancer cells from the immune response. The aim of the study was to assess whether the presence of TRAIL protein correlates with unfavourable prognostic factors in breast carcinoma. Material and methods The study group was composed of breast cancer patients treated surgically in the Department of Surgical Oncology, Medical University of Lodz, Poland, from January to December 2003. Inclusion criteria for the study were fulfilled by 117 women. The immunohistochemical study of TRAIL protein expression was performed in 118 breast carcinomas diagnosed in the study group. TRAIL protein expression was correlated with other variables: tumour size, lymph node status, grade, histological type of carcinoma, oestrogen and progesterone receptor status, HER2 expression, presence of lymphovascular invasion and age of the patient. Results Expression of TRAIL protein was present in 73% of breast carcinomas. The percentage of TRAIL-expressing breast carcinoma cells correlated with the nuclear grade (τ = 0.26, p < 0.05; Tau Kendall test). The intensity of TRAIL expression (intensity of staining) in breast carcinoma cells correlated with the nuclear grade (τ = 0.15, p < 0.05; Tau Kendall test). TRAIL expression in breast carcinoma did not correlate with other studied variables. Conclusions Our analysis revealed that expression of TRAIL protein in breast carcinoma cells correlates with nuclear grade of carcinoma.

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.

Is mastectomy with immediate breast reconstruction an alternative to breast-conserving treatment?

Mimo ze leczenie oszczedzające pierś uznawane jest za metode z wyboru w leczeniu chorych na wczesnego raka piersi, w niektorych badaniach zaobserwowano wzrost czestości wykonywanych mastektomii. Coraz cześciej w trakcie mastektomii wykonywana jest natychmiastowa rekonstrukcja piersi, mająca na celu zmniejszenie okaleczenia związanego z utratą piersi. Wykazano, ze zarowno leczenie oszczedzające pierś, jak i mastektomia z natychmiastową rekonstrukcją piersi są zabiegami bezpiecznymi onkologicznie i przynoszą porownywalny komfort zycia. Jednak zabieg mastektomii z rekonstrukcją natychmiastową piersi jest obarczony wiekszym odsetkiem powiklan pooperacyjnych, zwlaszcza w przypadku zastosowania radioterapii uzupelniającej. Dodatkową korzyścią leczenia oszczedzającego pierś jest mozliwośc odstąpienia od wykonania limfadenektomii pachowej w przypadku przerzutow ograniczonych do 1–2 wezlow wartowniczych, przez co chore mogą uniknąc powiklan związanych z usunieciem wezlow chlonnych pachowych. Ustalając plan leczenia chorych, nalezy zwrocic uwage na potencjalną przewage, jaką posiada leczenie oszczedzające pierś, nad mastektomią z rekonstrukcją natychmiastową pod wzgledem ryzyka wystąpienia powiklan.

Ex vivo Search for Sentinel Node in Postmastectomy Specimens: Should We Use a Transverse Incision for Mastectomy?

BackgroundAccording to the concept of sentinel node (SN), the lymphatic pathway leading to SN should be regarded as the main and the most important lymphatic route from primary tumor to regional lymph nodes. We performed ex vivo blue-dye SN mapping in postmastectomy specimens to assess whether the main lymphatic tract leading to SN is completely removed during mastectomy. We assumed that ex vivo identification of SN may be possible only if the entire lymphatic tract leading to sentinel node is removed from within the postmastectomy specimen.MethodsBlue dye (1 mL) was injected intracutaenously, periareolary into each of 28 postmastectomy specimens. In 13 cases mastectomy was performed with the use of transverse skin incision; in 15 cases oblique incision was used.ResultsThe use of transverse skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node only in 4 of 15 cases (31%). Conversely, the use of oblique skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node in 12 of 15 cases (80%).ConclusionsOur experiment revealed that the use of transverse skin incision during modified radical mastectomy may not be the best choice for breast cancer patients. In our opinion, this observation may be especially important for patients not irradiated postoperatively.