Ewa Śrutek

Frequent genetic differences between matched primary and metastatic breast cancer provide an approach to identification of biomarkers for disease progression.

Breast cancer is a major cause of morbidity and mortality in women and its metastatic spread is the principal reason behind the fatal outcome. Metastasis-related research of breast cancer is however underdeveloped when compared with the abundant literature on primary tumors. We applied an unexplored approach comparing at high resolution the genomic profiles of primary tumors and synchronous axillary lymph node metastases from 13 patients with breast cancer. Overall, primary tumors displayed 20% higher number of aberrations than metastases. In all but two patients, we detected in total 157 statistically significant differences between primary lesions and matched metastases. We further observed differences that can be linked to metastatic disease and there was also an overlapping pattern of changes between different patients. Many of the differences described here have been previously linked to poor patient survival, suggesting that this is a viable approach toward finding biomarkers for disease progression and definition of new targets useful for development of anticancer drugs. Frequent genetic differences between primary tumors and metastases in breast cancer also question, at least to some extent, the role of primary tumors as a surrogate subject of study for the systemic disease.

Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer

Sporadic breast cancer (SBC) is a common disease without robust means of early risk prediction in the population. We studied 282 females with SBC, focusing on copy number aberrations in cancer-free breast tissue (uninvolved margin, UM) outside the primary tumor (PT). In total, 1162 UMs (1-14 per breast) were studied. Comparative analysis between UM(s), PT(s), and blood/skin from the same patient as a control is the core of the study design. We identified 108 patients with at least one aberrant UM, representing 38.3% of cases. Gains in gene copy number were the principal type of mutations in microscopically normal breast cells, suggesting that oncogenic activation of genes via increased gene copy number is a predominant mechanism for initiation of SBC pathogenesis. The gain of ERBB2, with overexpression of HER2 protein, was the most common aberration in normal cells. Five additional growth factor receptor genes (EGFR, FGFR1, IGF1R, LIFR, and NGFR) also showed recurrent gains, and these were occasionally present in combination with the gain of ERBB2. All the aberrations found in the normal breast cells were previously described in cancer literature, suggesting their causative, driving role in pathogenesis of SBC. We demonstrate that analysis of normal cells from cancer patients leads to identification of signatures that may increase risk of SBC and our results could influence the choice of surgical intervention to remove all predisposing cells. Early detection of copy number gains suggesting a predisposition toward cancer development, long before detectable tumors are formed, is a key to the anticipated shift into a preventive paradigm of personalized medicine for breast cancer.

(18)F-FLT PET/CT in Patients with Gastric Carcinoma.

The aim of the study was to evaluate the usefulness of 18F-FLT PET/CT in the detection and differentiation of gastric cancers (GC). 104 consecutive patients (57 cases of adenocarcinoma tubulare (G2 and G3), 17 cases of mucinous adenocarcinoma, 6 cases of undifferentiated carcinoma, 14 cases of adenocarcinoma partim mucocellulare, and 10 cases of end stage gastric cancer) with newly diagnosed advanced gastric cancer were examined with FLT PET/CT. For quantitative and comparative analyses, the maximal standardized uptake value (SUVmax) was calculated for both the tumors and noninvaded gastric wall. Results. There were found, in the group of adenocarcinoma tubulare, SUVmax 1.5–23.1 (7.46 ± 4.57), in mucinous adenocarcinoma, SUVmax 2.3–10.3 (5.5 ± 2.4), in undifferentiated carcinoma, SUVmax 3.1–13.6 (7.28 ± 3.25), in adenocarcinoma partim mucocellulare, SUVmax 2–25.3 (7.7 ± 6.99), and, in normal gastric wall, SUVmax 1.01–2.55 (1.84 ± 0.35). For the level of 2.6 cut-off value between the normal wall and neoplasm FLT uptake from ROC analysis, all but five gastric cancers showed higher accumulation of FLT than noninfiltrated mucosa. Conclusion. Gastric cancer presents higher accumulation of 18F-FLT than normal, distended gastric mucosa. Significantly higher accumulation was shown in cancers better differentiated and with higher cellular density.

Core-needle biopsy under CT fluoroscopy guidance and fine-needle aspiration cytology: Comparison of diagnostic yield in the diagnosis of lung and mediastinum tumors. Analysis of frequency and types of complications

Summary Background Patients with pathological tissue mass in thoracic cage found with imaging require histopathological or cytological confirmation of malignancy before treatment. The tissue material essential for patomorphological evaluation can be acquired with fine-needle aspiration biopsies (FNAB) controlled with CT and core-needle biopsy (CNB) under real-time CT fluoroscopy guidance. The purpose of this work is to carry out a retrospective analysis of the two methods with regards to their informativity, frequency and the kind of complications. Material/Methods From January, 2012 to May 2013, 76 core-needle biopsies of lung and mediastinum tumors were conducted and compared with 86 fine-needle aspiration biopsies(FNAB) of lung and mediastinum tumors, including 30 patients who underwent FNAB and were referred to CNB in order to specify the diagnosis. Results Complete histopathological diagnosis was made in 91% with the use of CNB and in 37% when FNAB was the chosen method. Early complications were observed in 32% patients who underwent BG and in group of 11% who underwent FNAB. Late complications, however, appeared in 29% patients after CNB and 13% after FNAB. In 24 cases CNB specified the complete diagnosis. Conclusions Core-needle biopsy in comparison to fine-needle aspiration biopsy has more frequent rate of negligible complications, however, it offers higher diagnostic yield for diagnostic of lung and mediastinum neoplastic disease and allows for more precise diagnosis of focal lesions.

Current guidelines on the diagnosis and management of lobular carcinoma in situ

© Medical Communications Sp. z o.o. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (CC BY-NC-ND). Reproduction is permitted for personal, educational, non-commercial use, provided that the original article is in whole, unmodified, and properly cited. Current guidelines on the diagnosis and management of lobular carcinoma in situ Aktualne zalecenia dotyczące diagnostyki i leczenia chorych z rozpoznaniem raka zrazikowego piersi in situ

A study on the use of positron emission computed tomography analysis in recurrent colorectal cancer

Wstęp: Rak jelita grubego jest najczęstszym nowotworem złośliwym w Europie i Stanach Zjednoczonych. Nawet po doszczęt nym wycięciu guza pierwotnego wznowa choroby nowotworowej pojawia się u około 30% pacjentów. Cel: Ocena przydatności pozytonowej emisyjnej tomografii komputerowej (positron emission tomography/computed tomography – PET/CT) z wykorzystaniem 18-fluorodeoksyglukozy (FDG) w diagnostyce wznów miejscowych i przerzutów raka jelita grubego oraz odniesienie się do zależności pomiędzy wielkością wychwytu FDG a wynikami histopatologicznymi. Materiał i metody: Retrospektywnej analizie poddano 75 gu zów pochodzących od 59 chorych ze wznową lub przerzutem raka jelita grubego. Przed operacją u pacjentów wykonano badanie PET/CT. Wyniki tego badania określono za pomocą maksymalnej standardowej wartości wychwytu glukozy (SUVmax) w guzie. Wyniki: Czułość metody PET/CT w przypadku raka jelita grubego obliczono statystycznie i wyniosła ona 92%. Ujemne wyniki tego badania zależą od występowania zmian martwiczych (p < 0,01). Wartość SUVmax w guzach bez zmian martwiczych była istotnie statystycznie większa niż w guzach ze zmianami martwiczymi (p < 0,01). W przypadku guzów usuniętych u pacjentów z pierwotną lokalizacją choroby nowotworowej w odbytnicy SUVmax była istotnie statystycznie mniejsza niż u pacjentów z pierwotną lokalizacją guza w okrężnicy (p < 0,05). Wartość SUVmax w guzach zlokalizowanych w wątrobie jest istotnie statystycznie większa niż w guzach zlokalizowanych w płucach (p < 0,05). Nie stwierdzono w badanej grupie korelaAbstract