The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. MATERIALS AND METHODS: The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. RESULTS: The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). CONCLUSION: Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

Expression of ELF1, a lymphoid ETS domain-containing transcription factor, is recurrently lost in classical Hodgkin lymphoma.

Loss of B cell-specific transcription factors (TFs) and the resulting loss of B-cell phenotype of Hodgkin and Reed-Sternberg (HRS) cells is a hallmark of classical Hodgkin lymphoma (cHL). Here we have analysed two members of ETS domain containing TFs, ELF1 and ELF2, regarding (epi)genomic changes as well as gene and protein expression. We observed absence or lower levels of ELF1 protein in HRS cells of 31/35 (89%) cases compared to the bystander cells and significant (P < 0·01) downregulation of the gene on mRNA as well as protein level in cHL compared to non-cHL cell lines. However, no recurrent loss of ELF2 protein was observed. Moreover, ELF1 was targeted by heterozygous deletions combined with hypermethylation of the remaining allele(s) in 4/7 (57%) cell lines. Indeed, DNA hypermethylation (range 95-99%, mean 98%) detected in the vicinity of the ELF1 transcription start site was found in all 7/7 (100%) cHL cell lines. Similarly, 5/18 (28%) analysed primary biopsies carried heterozygous deletions of the gene. We demonstrate that expression of ELF1 is impaired in cHL through genetic and epigenetic alterations, and thus, it may represent an additional member of a TF network whose downregulation contributes to the loss of B-cell phenotype of HRS cells.

[Screening studies--is tobacco smoking always recognized as a risk factor?]. / Badania przesiewowe--czy palenie tytoniu jest zawsze uznawane za czynnik ryzyka?

There were introduced several screening programs for the early detection of neoplasms. They were devoted for diagnosis of cancer at early stage which gives a greater chance for totall recovery from the disease. The screening protocols include proper taking patient's history and then phisical examination with possibility of taking samples for histological evaluation. In this paper the authors on the example of screening of gynecological cytolotogy would like discuss the problem of lack of proper patients' history especially according the smoking habit.

Muscle-invasive urothelial cell carcinoma of the human bladder: multidirectional differentiation and ability to metastasize.

Few published studies have addressed the correlation between multidirectional differentiation in muscle-invasive bladder cancer and its ability to metastasize. We demonstrated that histologic differentiation within a single tumor affects lymph node metastasis. We examined cystectomy specimens from 93 bladder tumors and 1085 lymph nodes. In this study, urothelial cell carcinomas (UCCs) with divergent differentiation, excluding pure divergent patterns such as squamous cell carcinoma and adenocarcinoma that tend toward a distinct biologic behavior, were subjected to histopathologic estimation. The positive lymph node ratio increased with the nonconventional differentiation number (NDN) within a tumor from 8.7% for an NDN of 0 (pure conventional UCCs) to 35.5% for an NDN of 2 or higher (mixed conventional and nonconventional [NC] UCCs showing >2 NC patterns). The positive lymph node number (PLN) was more than twice as high for an NDN of 3 or higher as compared with cases with an NDN of 0. Lymph node positivity (LP) was associated with the presence of micropapillary, lymphoma-like, plasmacytoid, giant cell, or clear cell-type tumors, and increasing PLN was associated with the presence of glandular, nested, lymphoma-like, plasmacytoid, or undifferentiated types in the primary tumor. By multivariate analysis, NDN status was determined to be an independent predictor of PLN (P = .032). Tumor stage had impact on LP (P = .002); however, in cases with a PLN of 4 or higher, the NDN became the only predictor of further dissemination (P = .016). No significant tumor grade impact on LP or PLN was found. Our results indicate that NC differentiation in the primary tumor is a good predictor of lymph node dissemination.

[Cervical cytology picture--tobacco smoking and inadequate patients' history taking]. / Obraz rozmazów cytologicznych z szyjki macicy--wplyw palenia tytoniu oraz niedostatki badania podmiotowego.

Cardio-vascular diseases as well as neoplasms (especially upper respiratory cancer and lung cancer) the most commonly mentioned consequences of tobacco smoking. But among tobacco-related diseases there are several other conditions including cervical cancer. In the present study we included 1166 females who underwent gynecological cytology examination at Obstetrical and Gynecological Office in University Hospital in Bydgoszcz from January till June 2007. All samples were stained according to Papanicolaou procedure and evaluated according to Bethesda classification. We analyzed also information regarding smoking habit which should be included in patients' form. In our studies we found that in 67% of cases physicians did not indicate patients' smoking status. According to patients records we received only 3% were smokers while 30% were non-smokers. In cytological smears from smokers we found about 3 times higher incidence of high grade lesions comparing with non-smokers (6% vs. 1.7%). However, atrophic and inflammatory changes were more often fund among non-smokers (30% vs. 18%). In conclusion, we can state, that in almost 70% of studied cases smoking habit information was ignored by clinicians. Lesions with high risk of cervical cancer were found more commonly in smoking patients.

Usefulness of histologic homogeneity estimation of muscle-invasive urinary bladder cancer in an individual prognosis: a mapping study.

OBJECTIVES: To examine the histologic homogeneity of muscle-invasive urothelial cell carcinoma of the bladder, with conventional and nonconventional (eg, squamous, glandular, or variants) differentiation, to assess its influence on prognosis. METHODS: With organ mapping, we investigated 38 cystectomy specimens. Each entire bladder was cut into 88 slices according to an identical topographic scheme. From all the bladder slices, 1231 slices that included tumor were chosen for the histologic study. We examined the diagnostic significance, extension, and number of histologic differentiation types. RESULTS: The extension of nonconventional differentiation, with any proportion of histologic type, had an unfavorable impact on survival time. The number of nonconventional differentiation types increases in the presence of a sarcomatoid, an undifferentiated, a nested, or a micropapillary pattern. The increased number of differentiation types had an unfavorable influence on survival time. Patients with a more than 80% classic urothelial cell carcinoma pattern had a favorable prognosis, which increased further with increasing percentages of this differentiation type. CONCLUSIONS: Muscle-invasive urinary bladder cancers are not a homogenous group of tumors. Our results suggest that a precise assessment of the extension and number of histological differentiation types may be an individual prognostic factor. Conventional differentiation with at least 80% extension seems to be prognostically favorable. Nonconventional differentiation, especially with greater extension and a greater number of types, could imply a worse prognosis.