Intra-tumoral distribution of Ki-67 and Cyclin D1 in ER+ mammary carcinoma: quantitative evaluation

BackgroundIn spite of the strong evidence demonstrating the role of overexpression of Ki-67 and Cyclin D1 markers in breast carcinomas, clinical and pathological data remain to be discussed. This can be explained partly by intratumor heterogeneity.ObjectivesTo define the prevalence and clinical significance of Ki-67 and Cyclin D1 overexpression in primary breast tumors ER positive, while highlighting the existence of intratumor heterogeneity in this type of cancerMaterials and methods51 ER positive breast cancer tumors were used to evaluate the intratumoral distribution of Ki-67 and Cyclin D1 expression. Image acquisition and visualization of the markers were performed by optical microscopy and stereology sampling method.ResultsThe mean Ki-67 labeling index was distributed heterogeneously in the same tumor, from 20.67±6.87 to 45.10±10.65. The coefficient of variation (COV) revealed dispersion values between 13.4% and 42.9%. Associated with positive ER status, all the tumors presented a Cyclin D1 expression with a COV varying between 19% and 28.5% and a mean labeling index fluctuating between 19.40±4.42 and 41.64±10.08 within the same patient showing important intratumor heterogeneous distribution.ConclusionIn this study, we have adopted a strictly quantitative approach to evaluate and demonstrate intratumor heterogeneity. This establishes one of the main factors for poor response to cancer therapy. To achieve this, intratumor heterogeneity should be usually definable and quantifiable but this domain awaits future progress and methods need to move towards a better understanding of molecular and cellular mechanisms that initiate and maintain this tumor heterogeneity.     

The Insulin-Like Growth Factor Receptor I Promotes Motility and Invasion of Bladder Cancer Cells through Akt- and Mitogen-Activated Protein Kinase-Dependent Activation of Paxillin

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. Aberrant IGF-IR signaling is implicated in several types of tumors, including carcinomas of the lung, breast, prostate, pancreas, liver, and colon. However, the contribution of the IGF-IR to the development of the transformed phenotype in urothelial cells has not been clearly established. In this study we demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues compared with nonmalignant controls. We have investigated the role of the IGF-IR in bladder cancer by using urothelial carcinoma-derived 5637 and T24 cells. Although activation of the IGF-IR did not appreciably affect their growth, it did promote migration and stimulate in vitro wound closure and invasion. These effects required the activation of the Akt and Mitogen-activated protein kinase (MAPK) pathways as well as IGF-I-induced Akt- and MAPK-dependent phosphorylation of paxillin, which relocated at dynamic focal adhesions and was necessary for promoting motility in bladder cancer cells. Our results provide the first evidence for a role of the IGF-IR in motility and invasion of bladder cancer cells and support the hypothesis that the IGF-IR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia. Thus, the IGF-IR may also serve as a novel biomarker for bladder cancer.Bladder cancer is a major epidemiological problem, whose incidence continues to rise each year. The most recent cancer statistic¹ has estimated 68,810 new cases with 14,100 estimated deaths in the United States.Bladder tumors show widely differing histopathological and clinical behavior,² and this is a key problem in the management of bladder tumors. The majority of bladder tumors (∼70%) are low-grade noninvasive papillary tumors that do not penetrate the epithelial basement membrane (Ta stage). The remainder comprises tumors that have penetrated the basement membrane but not invaded the muscle layer of the bladder wall (T1 stage) and muscle-invasive tumors (T2, T3, and T4 stages).³The insulin-like growth factor receptor I (IGF-IR) plays a critical role in cell growth both in vitro⁴ and in vivo.⁵ Mice with targeted ablation of the IGF-IR gene have severe growth retardation, being only 45% the size of wild-type littermates, and die shortly after birth primarily due to respiratory failure.^6,7 These data suggest that the IGF-I/IGF-IR axis is critical for normal growth.The importance of the IGF-IR in transformation was initially suggested by experiments performed with cells derived from the IGF-IR-deficient mice. These cells were refractory to transformation induced by several tumorigenic agents (viral oncogenes, including Ras, SV40 large T Ag and overexpressed platelet-derived growth factor receptor and epidermal growth factor receptor, and various chemical agents) but were transformed when the IGF-IR was re-expressed.^8,9 In vitro experiments on tumor cell lines and epidemiological studies have confirmed that activation of the IGF-IR is involved in the development of many common neoplastic diseases, including carcinomas of lung, prostate, pancreas, liver, colon, and breast.^8,10,11 The transforming capability of the IGF-IR most likely depends on its ability to protect cancer cells from apoptosis.^12,13,14,15The IGF-IR has now become a very attractive target for cancer therapy, and in fact antibodies against the IGF-IR are currently in phase I clinical trials.^16,17 Whether the IGF-IR contributes to the transforming phenotype of urothelial cells has not been clearly established, but recent data suggest that the IGF-IR is overexpressed in bladder cancer.¹⁸In this study, using 5637 and T24 urothelial carcinoma-derived cells, we established that activation of the IGF-IR plays a critical role in bladder cancer by promoting migration, wound healing, and invasion of cancer urothelial cells. We have also characterized the mechanism of action of the IGF-IR in cancer urothelial cells and showed that IGF-IR-dependent cell motility and invasion required the activation of the Akt and MAPK pathway and Akt- and Extracellular-signal-related kinase 1 (ERK)-dependent activation of paxillin.Collectively, these results provide novel information toward a better understanding of the mechanisms that regulate tumor formation in bladder cancer at the cellular and biochemical level and suggest that the IGF-IR may be critical for bladder cancer.     

Cutaneous presentation of aleukemic monoblastic leukemia cutis - a case report and review of literature with focus on immunohistochemistry

Aleukemic monoblastic leukemia cutis is a rare cutaneous manifestation of a systemic hematological disorder associated with dermal infiltration of monoblasts preceding bone marrow or peripheral blood involvement. We report a case of a 75-year-old woman who presented with an erythematous maculopapular rash, which was clinically diagnosed as viral exanthema. Microscopy of the skin biopsy showed features of monoblastic leukemia. Her general physical condition rapidly deteriorated and she died 4 weeks later. We present this case to alert dermatologists of innocuous erythematous skin lesions clinically resembling a viral exanthema, which, in rare instances, may be a presenting feature of an aleukemic monoblastic leukemia cutis. This entity poses problems for dermatopathologists even on immunohistochemistry as monoblasts are negative for hemopoietic precursor cell antigens like CD34, Terminal deoxynncleotidy1 transferase (TdT) and CD117.     

Comparative Analysis of Vaginal Microbiota in Women with Breast Cancer in Kazakhstan

Object: The relevance of the article is that the breast cancer is a leading oncological disease in women in developed countries and has the highest mortality caused by malignant neoplasms in women. The purpose of the study is to evaluate vaginal microbiota in women with various breast cancer subtypes and compared groups. Methods: The study involved 278 women with breast cancer, of whom 174 were patients receiving combination therapy; the control group consisted of 104 patients who had had breast cancer 2-4 years ago. Results: It was found that despite a significant decrease in the total number of Lactobacillus spp., there were no statistically significant changes in the numbers of microorganisms in patients with different subtypes of breast cancer. According to the results of the comparative analysis, the representatives of obligate anaerobic flora Peptostreptococcus spp. prevailed in vaginal microbiota in luminal A and luminal B subtypes, and the representative of the facultative anaerobic organisms Staphylococcus spp. – in unfavourable outcomes in Her2/Neu+ and triple-negative subtypes. Conclusion: The observed features of the vaginal microbiota in women with different subtypes of breast cancer require further studies for preventive purposes.     

Deep learning for ultra-widefield imaging: a scoping review

Graefe's Archive for Clinical and Experimental Ophthalmology - This article is a scoping review of published and peer-reviewed articles using deep-learning (DL) applied to ultra-widefield (UWF)...     

Combined effects of salinity and temperature on some morphological aspects of four zoosporic fungi

The quantitative and qualitative formation and deformations of vegetative mycelia, zoosporangia and their discharge, oogonia, antheridia, gemmae, resting sporangia and male and female gametangia varied according to variations in NaCl concentration, temperature and incubation period. Species-dependent differences were observed.     

Papillary thyroid carcinoma in a 4-year-old boy

We present a case of Papillary Thyroid Carcinoma (PTC) in a 4- year- old boy. The very young age of the patient and unusual presentation with respiratory distress prompted us to report this case.