Endometriosis

Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis—the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed “vasculogenic mimicry” to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases.

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Vasculogenic Mimicry and Tumor Angiogenesis

SUMMARY Dirofilariasis represents a zoonotic mosaic, which includes two main filarial species (Dirofilaria immitis and D. repens) that have adapted to canine, feline, and human hosts with distinct biological and clinical implications. At the same time, both D. immitis and D. repens are themselves hosts to symbiotic bacteria of the genus Wolbachia, the study of which has resulted in a profound shift in the understanding of filarial biology, the mechanisms of the pathologies that they produce in their hosts, and issues related to dirofilariasis treatment. Moreover, because dirofilariasis is a vector-borne transmitted disease, their distribution and infection rates have undergone significant modifications influenced by global climate change. Despite advances in our knowledge of D. immitis and D. repens and the pathologies that they inflict on different hosts, there are still many unknown aspects of dirofilariasis. This review is focused on human and animal dirofilariasis, including the basic morphology, biology, protein composition, and metabolism of Dirofilaria species; the climate and human behavioral factors that influence distribution dynamics; the disease pathology; the host-parasite relationship; the mechanisms involved in parasite survival; the immune response and pathogenesis; and the clinical management of human and animal infections.

Human and Animal Dirofilariasis: the Emergence of a Zoonotic Mosaic

:CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally KIT is activated (phosphorylated) by binding of its ligand, the stem cell factor. This leads to a phosphorylation cascade ultimately activating various transcription fact

KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation.

We performed a meta-analysis of all 87 published studies linking intratumoral microvessel density (MVD), reflecting angiogenesis, to relapse-free survival (RFS) and overall survival (OS). With median MVD as cutoff, MVD impact was measured by risk ratio (RR) between the two survival distributions. Seventeen studies did not mention survival data or fit inclusion criteria. Twenty-two were multiple publications of the same series, leaving 43 independent studies (8936 patients). MVD was assessed by immunohistochemistry, using antibodies against factor VIII (27 studies; n = 5262), CD31 (10 studies; n = 2296), or CD34 (8 studies; n = 1726). MVD might be a better prognostic factor when assessed by CD31 or CD34 versus factor VIII (P = 0.11). For RFS, statistical calculations were performed in 25 studies (6501 patients). High MVD significantly predicted poor survival [RR = 1.54 for RFS and OS with the same 95% confidence interval (CI), 1.29-1.84]. Twenty-two studies analyzed separately lymph node-negative patients (n = 3580), for whom predictors of poor survival are requested. This latter meta-analysis included 15 studies for RFS (2727 patients) and 11 for OS (1926 patients). High MVD significantly predicted poor survival [RR = 1.99 for RFS (95% CI, 1.33-2.98) and RR = 1.54 for OS (95% CI, 1.01-2.33)]. Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cutoff selection. MVD was a significant although weak prognostic factor in women with breast cancer. Standardization of MVD assessment is needed.

https://cancerres.aacrjournals.org/content/canres/64/9/2941.full.pdf

Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis.

Background: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. Aims: To investigate KIT expression in normal and neoplastic renal tissues. Methods: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. Results: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. Conclusion: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications.

https://jcp.bmj.com/content/jclinpath/57/5/463.full.pdf

KIT expression in fetal, normal adult, and neoplastic renal tissues.

Recent experimental and clinical studies suggest that tumour-induced angiogenesis may be an important step in the evolution of malignant tumours, and may be related to prognosis. In our study we examined 42 cases of breast carcinoma (mean age: 56.76 +/- 13.5), 21 with lymph node metastases and 21 without. Angiogenesis was evaluated after immunohistochemical staining of tumour vessels, using polyclonal antibody to factor VIII related antigen (VIIIR-Ag) and counting of the three most active areas of neovascularization. In the same manner we counted the microvessels in lymph node metastases. The mean vessel count of node-negative cases (51.16 +/- 19.32) did not differ significantly from node-positive cases (45.66 +/- 17.44). In contrast patients younger than 50 years had much higher mean vessel counts (54.04 +/- 16.47) than did patients older than 70 years (38.03 +/- 16.73) producing a P value of < or = 0.05. No association was found between tumour size and mean vessel count, nor was there any significant difference between grade I (45.94 +/- 16.54), grade II (53.13 +/- 23.22) and grade III tumours (51.71 +/- 20.64). When we compared the mean vessel count of primary tumours with those of node metastases, we found much lower counts in the latter (P < or = 0.01). The differences in our results from previous studies, probably reflect the heterogeneity which exists between different tumours in their ability to induce angiogenesis. Additionally, there is some evidence in our study that angiogenesis is possibly related to patient age and probably depends on differences in the tumour stroma.

Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance?

The polymorphism of codon 72 in the p53 tumour suppressor gene has been associated in the last decade with the risk of developing various neoplasias. An influence of this polymorphism on ovarian and endometrial cancer has also been suggested. We examined the genotype frequency of this polymorphism i

P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women

Detection and Typing of Human Papillomavirus DNA in Uterine Cervices With Coexistent Grade I and Grade III Intraepithelial Neoplasia: Biologic Progression or Independent Lesions?

Ovarian pregnancy is a rare variant of ectopic implantation. A case of an intrafollicular ovarian pregnancy after ovulation induction/intrauterine insemination is presented. The woman had primary infertility of 4 years. Diagnostic laparoscopy revealed endometriosis and adhesions. After adhesiolysis and laser vaporization of endometriotic implants, the patient underwent ovulation induction with artificial insemination by husband/intrauterine insemination; she conceived at her second attempt. The pregnancy proved to be an ovarian intrafollicular one. She was treated by right partial ovariectomy. Three months later she conceived spontaneously with an intrauterine pregnancy which is still ongoing. The diagnostic problems resulting from the coexistence of ovarian hyperstimulation and the intrafollicular development of pregnancy are discussed. A re-evaluation of the criteria for the diagnosis of ovarian pregnancy based on the currently available diagnostic methods is proposed. Moreover, the pathophysiology of ovarian and especially intrafollicular implantation is reviewed.

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Dimosthenis Miliaras

Papers

KIT expression in fetal, normal adult, and neoplastic renal tissues.

Angiogenesis in invasive breast carcinoma: is it associated with parameters of prognostic significance?

P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women

Detection and Typing of Human Papillomavirus DNA in Uterine Cervices With Coexistent Grade I and Grade III Intraepithelial Neoplasia: Biologic Progression or Independent Lesions?

Intrafollicular ovarian pregnancy after ovulation induction/intrauterine insemination: pathophysiological aspects and diagnostic problems.