Darius Pranys

Distribution of CD4+ and CD8+ T cells in tumor islets and stroma from patients with non-small cell lung cancer in association with COPD and smoking

BACKGROUND AND OBJECTIVE The immune system plays an important role in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the infiltration patterns of CD4(+) and CD8(+) T cells in NSCLC and to analyze their relation to COPD, smoking status and other clinicopathologic variables. MATERIALS AND METHODS Lung tissue specimens from 50 patients who underwent surgery for NSCLC (stages I-III) and 10 control group subjects were analyzed immunohistochemically. RESULTS NSCLC patients had a greater number of CD4(+) and CD8(+) T cells infiltrating the lung tissue than the control group (P=0.001) with predominant infiltration in the tumor stroma. We found a significant association between the number of total and tumor stroma-infiltrating CD4(+) and CD8(+) T cells, and smoking status (P<0.05). There were more CD8(+) T cells in the tumor stroma and fewer in the tumor islets in NSCLC patients with COPD as compared to NSCLC patients without COPD (P<0.05). However, there was no such association between CD4(+) T cells and COPD status. A high level of CD8(+) T cell infiltration in the tumor stroma was independently associated with the coexistence of COPD in multivariate analysis (P<0.05). CONCLUSIONS According to our data, COPD but not smoking seems to be associated with higher infiltration of CD8(+) T cells in the tumor stroma of patients with NSCLC. It allows us to hypothesize that NSCLC patients with coexisting COPD may have a more favorable outcome due to anticancer properties of stromal CD8(+) T cells.

A 10-month-old boy with a large pineal tumor.

February 2005. Case report of a 10‐month‐old boy with a large tumor located in the pineal gland, consisting of glia, ganglion cells, pigmented neuroepithelium and striated muscle, without immature components. The combination of neuroectodermal and mesenchymal constituents includes entities as pineal anlage tumor (melanotic neuroectodermal tumor of infancy, MNTI), ectomesenchymoma, medullomyoblastoma, and teratoma in the differential diagnosis. Lack of immature elements in this case, however, eliminates ectomesenchymoma and medullomyoblastoma from the differential diagnosis. Retinal anlage tumors, to be considered as MNTI at the site of the pineal gland, usually harbor immature components as well. Therefore, the present case does not match strict criteria of any of the categories mentioned and therefore we have designated it as a “pineal anlage tumor (without immature components)”.

The Association of Low-To-Moderate Alcohol Consumption with Breast Cancer Subtypes Defined by Hormone Receptor Status

Background Alcohol is a well-established risk factor for breast cancer, but pathways involved in alcohol-related breast carcinogenesis are not clearly defined. We examined the association between low-to-moderate alcohol intake and breast cancer subtypes by tumor hormone receptor status. Materials and Methods A hospital-based case-control study was performed in 585 cases and 1,170 controls. Information on alcohol intake and other risk factors was collected via a questionnaire. Logistic regression was used for analyses. All statistical tests were two-sided. Results The odds ratio of breast cancer was 1.75 (95% confidence interval [CI]: 1.21–2.53) in women who consumed ≤5 drinks/week, and 3.13 (95% CI: 1.81–5.43) in women who consumed >5 drinks/week, both compared with non-drinkers for ≥10 years, after adjustment for age and other confounders. The association of alcohol intake with estrogen receptor-positive breast cancer was stronger than with estrogen receptor-negative: the odds ratio per 1 category increase was 2.05 (95% CI: 1.49–2.82) and 1.29 (95% CI: 0.85–1.94) (P-heterogeneity = 0.07). There was no evidence of an interaction between alcohol intake and menopausal status (P = 0.19) in overall group; however, it was significant in estrogen receptor-positive breast cancer (P = 0.04). Conclusions Low-to-moderate alcohol intake is associated with the risk of estrogen receptor-positive breast cancer with the strongest association in postmenopausal women. Since alcohol intake is a modifiable risk factor of breast cancer, every woman should be informed and advised to control alcohol use.

Malignant Pleural and Peritoneal Mesothelioma: Incidental Diagnosis and Excellent Treatment Results

To the Editor: Patients with malignant pleural and peritoneal mesothelioma usually present with advanced symptomatic disease.1 Prognosis is poor. During our practice we had an exceptional mesothelioma case. During cholecystectomy peritoneal biopsy was done due to infiltration of omentum for 56-year-old man. The biopsy analysis showed that patient had peritoneal mesothelioma (Figure 1). The second mesothelioma marker WT-1 was positive and other markers (CEA, CD-15, and TTF-1) were negative. There were no respiratory symptoms or history of asbestos exposure. The patient (former smoker) was in good functional status. Chest computed tomography (CT) scan revealed multinodal lesions of left pleura (Figure 2). Malignant pleural and peritoneal mesothelioma was diagnosed and treatment with permetrexed 500 mg/m day 1 and cisplatin 80 mg/m day 1 (for 1 cycle) every 21 day was prescribed. The patient was assessed regularly with chest and abdomen CT (according to the modified RECIST criteria2). The pleural signs of mesothelioma disappeared completely after six cycles. No pleural or peritoneal changes were seen on CT scan 6 months after completion of chemotherapy (Figure 3). The patient is still alive with no signs of disease progression 3 years later. Early retrospective studies reported 5-year survival rates of 1% and overall median survivals of 7.6 months for patients not receiving chemotherapy. Eight randomized clinical trials concerning the mesothelioma chemotherapy have been published. Vogelzang et al.3 treated 448 eligible patients with either permetrexed and cisplatin or cisplatin alone. Response rates (41%versus 17%, p was 0.001), time to progression (5.7 versus 3.9 months, p was 0.001), and survival (median, 12.1 versus 9.3 months; hazard ratio 0.77, p was 0.020) all favored the combination treatment. In another large phase III trial,4 250 patients were randomized to receive either raltitrexed and cisplatin or cisplatin alone. Overall response rates (24% versus 14%, p was 0.056) was greater in the combination treatment arm. Now permetrexed combined with platinum compound is the only recommended treatment for extensive mesothelioma. According to the data of clinical trials the complete response during first line chemotherapy in malignant pleural mesothelioma is extremely rare. Furthermore, we could not find any reported data concerning the complete response rate in randomized clinical trials with permetrexed treatDisclosure: The authors declare no conflicts of interest. Copyright

Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival.MethodsLung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually.ResultsPredominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05).ConclusionsThis study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients’ survival.Trial registrationClinicalTrials.gov NCT01955343, registered on September 27, 2013

Association between lifetime exposure to passive smoking and risk of breast cancer subtypes defined by hormone receptor status among non-smoking Caucasian women.

Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest that breast cancer risk is related to passive smoking, little is known about the association with breast cancer by tumor hormone receptor status. We aimed to explore the association between lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and progesterone receptor status among non-smoking Caucasian women. A hospital-based case-control study was performed in 585 cases and 1170 controls aged 28–90 years. Information on lifetime passive smoking and other factors was collected via a self-administered questionnaire. Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer was 1.01 (95% confidence interval (CI): 0.72–1.41) in women who experienced exposure to passive smoking at work, 1.88 (95% CI: 1.38–2.55) in women who had exposure at home, and 2.80 (95% CI: 1.84–4.25) in women who were exposed at home and at work, all compared with never exposed regularly. Increased risk was associated with longer exposure: women exposed ≤ 20 years and > 20 years had 1.27 (95% CI: 0.97–1.66) and 2.64 (95% CI: 1.87–3.74) times higher risk of breast cancer compared with never exposed (Ptrend < 0.001). The association of passive smoking with hormone receptor-positive breast cancer did not differ from that with hormone receptor-negative breast cancer (Pheterogeneity > 0.05). There was evidence of interaction between passive smoking intensity and menopausal status in both overall group (P = 0.02) and hormone receptor-positive breast cancer group (P < 0.05). In Caucasian women, lifetime exposure to passive smoking is associated with the risk of breast cancer independent of tumor hormone receptor status with the strongest association in postmenopausal women.

HER2 receptorių ir p53 baltymo padidėjusios raiškos įtaka II stadijos krūties vėžiu sergančių moterų gyvenimo trukmei

Tyrimo tikslas. Istirti p53 baltymo ir HER2 (c-erbB-2) receptorių padidėjusios raiskos įtaką II stadijos krūties vėžiu sirgusių jaunų moterų penkerių metų isgyvenamumui, atsižvelgiant į hormonų receptorių bei gydymo savitumų reiksme. Tyrimo medžiaga ir metodai. Retrospektyviai analizuojama 34 Kauno apskrities moterų, gydytų 2001–2003 m. Kauno onkologijos ligoninėje, medicininė dokumentacija ir archyvinė histologinė medžiaga. Tiriamųjų kontingentas – jaunos, iki 50 metų moterys, kurioms diagnozuotas ir morfologiskai patvirtintas II stadijos krūties vėžys. 22 moterys isgyveno penkerius metus, 12 mirė penkerių metų laikotarpiu. Panaudojant archyvine histologine medžiagą de novo, tuometinėje KMUK Patologinės anatomijos klinikoje buvo atliktas p53 baltymo ir HER2 receptorių raiskos tyrimas imunohistocheminiu metodu. Panaudojant medicinine dokumentaciją, analizuota pacientėms skirta adjuvantinė chemoterapija, antraciklinų suminė dozė ir hormoninis gydymas. Rezultatai. Tarp visų 34 tiriamųjų 20,6 proc. atvejų rasta padidėjusi p53 baltymo raiska, 26,4 proc. atvejų – HER2 baltymo raiska. Analizuojant isgyvenamumą Kaplan-Meier metodu, nustatyta, kad mirties tikimybė penkerių metų laikotarpiu didesnė, kai naviko histologinėje medžiagoje rastas padidėjes p53 baltymo kaupimasis, neigiami estrogenų receptoriai ir kai pacientės gydytos nepakankama antraciklino doze (log rank p=0,013, log rank p=0,02, log rank p=0,027, atitinkamai). Nerasta sąsajų tarp padidėjusios HER2 baltymo raiskos ir paciencių penkerių metų isgyvenimo (log rank p=0,51). Daugiamatės analizės metodu nustatyta, kad vienintelis nepriklausomas veiksnys yra nepakankama antraciklinų dozė (p=0,028). Isvada. Jaunų moterų, susirgusių II stadijos krūties vėžiu, trumpesnei gyvenimo trukmei įtakos turi padidėjusi p53 baltymo raiska, sumažinta antraciklinų dozė ir neigiami estrogenų receptoriai, o HER2 baltymo padidėjusios raiskos įtakos penkerių metų gyvenimo trukmei nepavyko įrodyti. Nepriklausomas prognozinis veiksnys yra nepakankamas adjuvantinis gydymas antraciklinais.