The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients.

INTRODUCTION: Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. OBJECTIVES: The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. METHODS: We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. RESULTS: There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. CONCLUSIONS: Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation.

EFFECT OF EXPERIMENTAL DYSGLYCEMIA ON UNDER-CARBOXYLATED OSTEOCALCIN PRODUCTION IN HUMAN PRIMARY OSTEOBLAST-LIKE CELL CULTURES.

CONTEXT: The undercarboxylated form of osteocalcin (ucOC) and osteoprotegerin (OPG) are bone-derived molecules involved in the endocrine crosstalk governing the bone, the adipose tissue and the pancreas. In addition, glucocorticoids are major determinants of both insulin resistance and osteoporosis. OBJECTIVE: We aimed to investigate the response of ucOC and OPG to dysglycemia and/or dexamethasone (DXM) in primary human osteoblastic cell (HOC) cultures. DESIGN AND METHODS: Third-passage sub-confluent primary HOC cultures were treated with glucose: 2.8 mmol/L, 5.6 mmol/L, 11.1 mmol/L and 28 mmol/L, respectively. Alternatively, HOC cultures were subjected to DXM 1 µmol/L. In more complex experiments, HOC cultures were pre-treated with glucose (5.6 mmol/L) with/without insulin (1 pmol/L) followed by DXM (1 µmol/L). 24-hours post-treatment, culture medium ucOC and OPG were measured by ELISA. RESULTS: ucOC production differed significantly (p<0.05) between cell groups, decreasing in a dose-dependent manner as glucose concentration in the medium increased. Insulin prevented this effect. OPG levels appeared not to be significantly influenced by the hyperglycemic culture medium and were not related to ucOC concentration (p>0.05). Addition of DXM resulted in significantly lower ucOC concentrations compared to vehicle-treated cells (p<0.05). However, the effect of insulin co-treatment on ucOC was not counteracted by DXM (p<0.05). CONCLUSIONS: An obvious alteration of OC production/metabolism was observed as glucose levels changed in the bone microenvironment, to potentially be involved in diabetes-related osteopenia. DXM suppressed ucOC levels however not in insulin-rich environment.

ASSOCIATION OF COL1A1 SP1 AND FOK-I VDR GENETIC POLYMORPHISMS IN YOUNG MALE IDIOPATHIC OSTEOPOROSIS.

INTRODUCTION: Primary osteoporosis during childhood and adolescence represents an uncommon condition, and secondary forms are more likely to manifest at this age due to chronic disease and adverse effects of medical treatment. CASE REPORT: The authors report the case of a young male patient with a history of multiple idiopathic non-vertebral fragility fractures in addition to a family history of maternal osteoporosis and fracture, in whom osteoporosis was confirmed according to 2013 International Society for Clinical Densitometry (ISCD) criteria. Bone markers indicated low bone formation marker osteocalcin. Genetic testing revealed homozygosity for Sp1 COL1A1 gene polymorphism in combination to Fok-I vitamin D receptor (VDR) heterozygous polymorphism, to contribute to low bone mass and increased fracture risk. Severe premenopausal osteoporosis was present in the patient's mother, who was also tested positive for both gene polymorphisms. CONCLUSION: This case report highlights the association between COL1A1 and VDR candidate gene polymorphisms and fragility fractures in a family. Individual genetic testing might be of clinical value in idiopathic osteoporosis in young patients, identifying subjects at increased fracture risk.

SURGERY OUTCOMES IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AND IMPACT OF INTRA-OPERATIVE PTH MEASUREMENT.

CONTEXT: The current therapeutical management of secondary hyperparathyroidism (S-HPTH) is difficult to obtain due to the lack of kidney donors. Surgical intervention on the pathologic parathyroid tissue has been suggested as a method to alleviate symptoms in patients with chronic kidney disease (CKD). OBJECTIVE: The aim of our study was to evaluate the outcomes of parathyroid surgery in patients with S-HPTH and the advantages of intraoperative quick PTH (iqPTH) to improve surgical results. MATERIAL AND METHODS: In a real-life study, we compared one group of S-HPTH with iqPTH performed after removing all suspected glands and before wound suture (Group 1) and one group in that iqPTH was not assessed (Group 2). When iqPTH dropped less than 50%, additional exploration followed. RESULTS: Eight out of the 34 patients from Group 1, who underwent subtotal parathyroidectomy, showed elevated levels of serum PTH and calcium, which remained elevated during follow-up, thus, suggesting disease persistence. From the 21 patients in Group 2, none showed early postoperative disease persistence. Serum calcium, but not PTH was increased in one patient from the iqPTH group but normalized after one month. Overall, iqPTH allowed detection of a supplementary parathyroid gland in one case, thereby increasing early post-surgery remission to 100% in Group 2 compared to 76.47% in Group 1. Late postoperative remission of hyperparathyroidism with no further increase in the rate of hypoparathyroidism was obtained in Group 2. CONCLUSIONS: Assessment of intra-operative PTH levels proved to be a useful tool in augmenting the outcome of S-HPTH surgery. In patients which are eligible for renal transplantation who undergo a subtotal resection, iqPTH can enhance the post-operative quality of life by lowering disease recurrence rates until the kidney transplant procedure.

Histopathological Study on Conservatively Operated Breast Carcinomas.

In this histopathological study we looked at 303 cases of breast carcinomas, managed though conservative breast surgery and later analysed with the help of a classical histopathological technique, paraffin embedding. The carcinomas were assessed in terms of tumor size, lymph node status, histological type, correlation between invasive tumors and an situ carcinoma component, resection margins, grading and patients age. Following assessment, we looked at associations between above morphological and clinical parameters and ipsilateral local recurrences. We concluded that more than half of our cases were carcinomas, measuring between 2 cm and 5 cm, with no associated lymph node involvement, in keeping with pTNM criteria for stage II. By far, in our study, the most frequent histopathological type was type NOS (63.37%) followed by invasive lobular carcinoma (10.56%) and mixed ducto-lobular invasive carcinoma (6.27%). Other types of invasive carcinoma were rarer, each representing less than 4% of cases. In regards to in situ carcinomas we noted the most common histological types to be both cribriform intraductal carcinoma and comedocarcinoma, each identified in 1.65% of cases. Amongst invasive breast carcinomas, infiltrating ductal carcinoma not otherwise specified (NOS) was found to be most commonly associated with in situ ductal carcinoma lesions. This was seen in 34.9% of cases, and was the only type associated with an extensive in situ component. Analysing the grading of mammary carcinomas in our study showed that the vast majority of cases (63.04%) were grade 3 tumors. In regards to surgical resection margins, ¾ of cases were noted to have negative margins. Tumor recurrences were noted in 12 cases. These cases were most commonly noted to reoccur following initial poorly differentiated, infiltrating ductal carcinomas, not otherwise specified (NOS), with positive resection margins, measuring less than 2 cm. Patiens tended to be under the age of 40 and had positive lymph nodes. The emergence of local recurrences after conservative surgery for early breast cancer is singnificantly linked to poorly differentiated primary tumors (p <0.05) but not correlated with histological type, presence of extensive intraductal carcinoma component, size of primary breast tumor or lymph node status ( p> 0.05). In terms of increasing the risk of ipsilateral recurrence the most important aspect highlighted in our sudy was the status of the resection margins. Patients with positive resection margins had a significantly high risk to develop recurrences after the conservative surgery, compared to those with negative margins (p <0.001).

VASCULAR ENDOTHELIAL GROWTH FACTOR SERUM LEVELS IN WOMEN WITH ADVANCED ENDOMETRIOSIS.

CONTEXT: Endometriosis is a common gynecological disease, characterized by ectopic deposits of endometrial tissue outside of the uterine cavity, and it is associated with pelvic pain and infertility, with an important impact on the quality of life. At this point there is a controversy regarding the etiology and pathophysiology of endometriosis and it seems that pro-angiogenic growth factors might be involved, but their role is not completely understood. OBJECTIVE: To evaluate the serum concentration of the main growth factors in patients with diagnosed endometriosis compared to healthy controls. SUBJECTS AND METHODS: A total of 157 women were divided into two study groups (Group I - endometriosis; Group 2 - healthy women). Serum levels of VEGF, G-CSF, GM-CSF, b-FGF, EGF, and HGF were measured with Human Multiplex Cytokine Panels. RESULTS: VEGF serum levels were significantly lower in women with endometriosis compared to controls (1.924±0.145 compared to 1.806±0.078 pg/mL, p<0.001). Serum levels of GM-CSF, b-FGF, EGF, and HGF respectively did not differ significantly between patients with endometriosis and healthy controls. G-CSF had a very low detection rate. CONCLUSIONS: The present study showed that VEGF serum levels are significantly lower in endometriosis patients compared to healthy controls, indicating a possible role in endometriosis pathogenesis.

Glycemic profile in patients with acromegaly treated with somatostatin analogue.

HYPOTHESIS: The growth hormone (GH) excess displayed in acromegaly induces insulin resistance up to diabetes mellitus (DM). The somatostatin analogues (as octreotide LAR) are useful in controlling the GH levels but disturbances of glucose metabolism might be seen. OBJECTIVE: This study evaluates the acromegalic glycemic profile under octreotide. METHODS & RESULTS: Out of the total number of patients (N=34) diagnosed with active acromegaly, only some were followed (N=25; male/ female ratio: 6/ 19; mean age: 51.8 years) by testing GH, IGF1 (Insulin Growth Factor 1), basal glucose and oral glucose tolerance test (OCGTT) at baseline, 6 and 12 months under Octreotide (first 6 months with 20 mg/ 28 days + 6 months with 30 mg/ 28 days). Pre-treatment values were 17.6% of patients had DM, 14.7% - impaired glucose tolerance, 26.5% - impaired fasting glucose, and 41.2% - normal assays. From the statistical point of view, the DM patients were significantly older and had higher GH levels than the acromegalic without glycaemia disturbances. They did not achieve significant changes in basal blood glucose and glycated hemoglobin after 6 months, neither after 12 months. After 6 months, there were no significant changes in basal glycaemia in patients with normal baseline glycaemia but 2-hours OGTT glucose values were significantly lower than initially (82.35 mg/ dl vs. 93 mg/ dl, p=0.005) consistent with reduced levels of GH and IGF1. After 12 months, both basal and 2-hours glucose levels in OGTT were similar to baseline despite the significant lower GH (3.3 vs. 6.61 ng/ mL, p=0.003) and IGF1 (332 vs. 713 ng/ mL, p=0.001). CONCLUSIONS: Octreotide therapy induces an improvement in glycemic profile in patients with active acromegaly without diabetes mellitus consistent with decreased levels of GH and IGF1. In patients with diabetes, partial control of glucose metabolism is due to inadequate suppression of GH and IGF1 after one year of treatment.

Clinical and Pathological Analysis of Two Cases of Cutaneous Malignant Melanoma.

The purpose of this study was the clinical and histo-immunohistochemical analysis of two cases: a cutaneous pigmented facial malignant melanoma and a lumbar congenital nevus with malignant transformation. A series of clinical elements raised the suspicion of some malignant melanocytic lesions and the histopathological analysis through the paraffin embedding technique confirmed the clinical suspicion. The immunohistochemical analysis using the streptavidin-biotin-peroxydase method of the facial malignant melanoma showed: S100 protein intense and diffuse positive, Tyrosinase diffuse positive, HMB45 strong and focal positive, Cyclin D1 positive in approximately 40% and Ki-67 positive in almost 70% of the tumor cells. The malignant melanoma developed on the nevocellular nevus displayed: S100 protein intense and diffuse positive, both in the nevus cells and in the malignant melanocytes as well, Tyrosinase intense and diffuse positive in the malignant melanocytes, poor and focal positive in the nevus cells and HMB45 intense and focal positive in the malignant cells and positive in the isolated nevus cells. Cyclin D1 was positive in about 70% of the malignant cells, but negative in the nevus area and Ki-67 was found positive in relatively 30% of the malignant melanocytes, also in less than 1% of the nevus cells. The pattern and the intensity of the Tyrosinase and HMB45 immunoexpression are important in the differentiation of the nevus cells from the malignant melanocytic cells. The immunoexpression of Cyclin D1 does not correlate directly with the proliferating activity of the malignant melanocytic cells in all types of malignant melanomas.

Current Role of Endoscopic Ultrasonography in Rectal Cancer Evaluation During Multidisciplinary Therapy.

We report the case of a patient presenting in the Gastroenterology Department with intermittent rectal bleeding during the past year. A diagnosis of a low rectal adenocarcinoma was based on colonoscopy examination with biopsies, and staging procedures included transrectal endoscopic ultrasonography and magnetic resonance imaging of the abdomen and pelvis (cT2N0M0). Consequently the patient was referred for pre-operative chemoradiotherapy, achieving a complete clinical response as documented by repeated EUS and MRI examinations. Transanal endoscopic microsurgery with pathological assessment of the resected specimen revealed residual adenocarcinoma, highlighting the limitations of current imaging methods, and the constant need of technological improvements.

Endomicroscopy with Fluorescent CD105 Antibodies for "In Vivo" Imaging of Colorectal Cancer Angiogenesis.

The aim of this case report was to evaluate the feasibility of in vivo acquisition of microscopic images using fluorescent CD105 antibodies for molecular imaging in human colorectal cancer. After excluding the presence of tissue autofluorescence, the antibody solution was topically administered through a spray-catheter. The targeted area was analyzed by eCLE and images were recorded. The fractal dimension of tumor vessels and the vessel density were determined using ImageJ software. Immunohistochemistry was used as a gold standard. In vivo CLE analysis of CD105 expression enabled the study of tumor vascular network, revealing a chaotic structure.

Cutaneous leiomyosarcoma - Case report.

Cutaneous leiomyosarcoma (CLM) is a very rare smooth muscle tumor arising from the dermis or subcutaneous tissue in the skin. Superficial leiomyosarcoma originates in the superficial dermis or subcutaneous tissue and represents about 3% of the soft tissue sarcomas. CLM presents in persons of all ages but with a peak between 60-70 years old. It may also occur anywhere on the body; the existing cases reported it on the face and trunk. The clinic of leiomyosarcoma consists in a firm dermal nodule, which can be painful, pruritic or paresthestic. The tumor is of 1-3 cm in diameter and can often be seen as a solitary formation. We report one case of a cutaneous leiomyosarcoma arising in the chest region of a 79- year-old male. Leiomyosarcoma is a rare entity whose clinical presentation may appear nonspecific, making diagnosis difficult. Primary tumor excision with wide oncological safety margins is considered, when suitable case, the most appropriate method. Other therapeutic methods, such as radio- or chemotherapy are described as without significant benefits. Despite the claims of radical surgical treatment, due to recurrence rates, the prognosis remains poor. We recommend long-term follow-up of patients to capture a subsequent malignant disease progression.

Prehepatocholedochal proper hepatic artery. Rare anatomical variant. Surgical considerations. Case report.

In classical anatomic variants, the proper hepatic artery (PHA)continues the common hepatic artery (CHA) after the gastroduodenal artery (GDA) detaches itself and divides into the right hepatic artery (RHA) and left hepatic artery (LHA), the proper hepatic artery being located to the left of the hepatocholedochal duct (HCD). This paper presents an abnormal positioning of the PHA placed before the HCD with an increased diameter of about 5-7 mm, which could be confused with the HCD. We present the case of a 57 year-old woman diagnosed with acute lithiasic cholecystitis, associated with hypersplenism and hypertension. The literature mentions manifold anatomical variants of arterial liver vascularization,including PHA. For this reason, this paper presents an overview of similar cases that can be found in medical literature. The aforementioned case is a rare topographic anatomy for the PHA that can easily pass for HCD especially during celioscopy, therefore it is crucial for this to be acknowledged by all surgeons.

Face Basosquamous Carcinoma, a Case Report.

Face basosquamous or metatypical carcinoma is a rare and controversial form of skin cancer. It is characterized by increased incidence of recurrence and distant metastases. We present the case of a patient of 71 years with an ulcerative lesion of 3/4 cm in the nasal pyramid. The injury occurred due to trauma to the nasal pyramid, produced 13 years ago. After investigation, which included ORL examination, imaging and oncology exam, surgery was decided to completely ablate tumor formation. The resulted defect of 4/5 cm was covered by mobilizing a forehead flap based on right supratrohleare artery pedicle. Histopathological examination revealed the diagnosis of basosquamous or metatypical carcinoma. The patient was referred to the oncology service for treatment.

Assessment of CD105, α-SMA and VEGF expression in gastric carcinomas.

In this study, we analyzed the microvessel density (MVD) for CD105+ and α-SMA+ vessels and the VEGF immunoexpression in 38 gastric carcinomas. CD105+ MVD had superior values at the advancing edge compared with the intratumoral area, no matter of the analyzed clinico-pathological parameters, the difference being significant only in intestinal type, moderate differentiated carcinomas as well as in T2-T3 carcinomas, without lymph node metastases (p<0.05). Intratumoral expression of CD105+ MVD indicated significant differences related to histological type (p=0.006), depth of invasion (p=0.027) and lymph node metastases (p=0.009), but without statistical association in case of the advancing edge or metastases. The assesses of α-SMA+ MVD indicated no differences between intratumoral and advancing edge areas, no matter of the analyzed parameters, excepting intestinal type carcinomas, which presented significant high values (p=0.003) at the advancing edge. VEGF score revealed significant differences related to histological type (p=0.020), differentiation degree of the intestinal type carcinomas (p=0.036) and depth of invasion (p=0.049). In case of metastases, the levels of VEGF expression were higher in the primary tumor, without statistically significant differences (p>0.05). It were significant differences of intratumoral VEGF expression depending on CD105+ MVD values (p=0.019), but not with α-SMA+ MVD (p>0.05). Angiogenesis evaluated through the VEGF and MVD (CD105+ and α-SMA+) expression is correlated with the progression and metastasis of gastric cancer and could be considered a prognostic marker of these tumors.

A rare case of acute abdomen: Garengeot hernia.

The association of acute appendicitis with femoral hernia,strangulated or incarcerated, represents a rare but well documented pathology in the specialized medical literature,also known as Garengeot hernia. The development of an acute appendicitis in the femoral hernia sac becomes a surgical emergency of acute abdomen. The diagnosis is always mistaken for the one of incarcerated or strangled hernia, the correct diagnosis being established intraoperatively, occasion which exposes the cecal appendix by opening the herniary bag, found in different morphological stages of inflammation that can go as far as gangrene or even perforation. In this paper, we have reported the case of a 76 year-old female that presented with femoral tumours, incarcerated, painful and initially considered as an incarcerated femoral hernia, the final diagnosis being made intraoperatively. The treatment for these "hernias" is generally simple, when there are no complications of acute appendicitis as the presence of pus in the hernia sac, and consists in appendectomy and herniorrhaphy. The absence of symptoms for an acute appendicitis often delays the surgery which leads to frequent complications and increased rate of morbidity.

Immunohistochemical expression of EGF, c-erbB-2 and EGFR in intestinal variant of gastric adenocarcinomas.

In this study, we aimed to determine EGF, c-erbB-2 and EGFR expression in 25 specimens of intestinal gastric adenocarcinomas by standardized immunohistochemistry and to establish correlations with the major clinico-morphological parameters of these patients. We observed EGF reactivity in 22 (88%) cases, a c-erbB-2 protein expression in eight (32%) cases and an EGFR reactivity in 13 (46.42%) cases. The EGF expression was significantly correlated with the tumor degree of differentiation, but not with other investigated clinico-morphological parameters and nor with c-erbB-2 and EGFR1 expression. However, we noticed the existence of a dependence between c-erbB-2 and EGFR1 expression in the main tumor mass. Such immunoprofile suggests the possible intervention of autocrine and paracrine loops in the developing of intestinal variant of gastric adenocarcinomas.

Multiple benign symmetric lipomatosis -- a differential diagnosis of obesity.

Benign symmetrical lipomatosis (BSL), or Madelung's disease, is a rare disease characterized by the progressive growth of diffuse, painless, non-enveloped symmetric lipomas. The etiology of this disease remains unknown, although it was associated in the medical literature with alcohol and nicotine abuse, metabolic disorders and a number of malignancies. It is assumed that there is a genetic predisposition for this affliction. The management in such cases is surgical removal of the lipomas, most times in several sessions, but this is often followed by relapse. However, surgical removal of the lipomas can provide satisfactory patient functionality and cosmetic results. The differential diagnosis is made with morbid obesity, Cushing syndrome, angiolipomatosis, encapsulated lipomas, neurofibromatosis, myxoid liposarcoma, lymphoma, salivary gland disease, Frolich and lipomatosis syndrome in patients infected with HIV. The current paper reports the case of a 55 year-old man, who presented with several large lipomatous masses, arranged symmetrically on the front and back of the trunk, and several smaller lipomas in the upper and lower limbs. Treatment consisted of resection of these lipomas in several sessions, without recurrence at one year after the last operation.

Lymphatic microvessels density, VEGF-C, and VEGFR-3 expression in 25 cases of breast invasive lobular carcinoma.

Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer, having distinct morphologically but also prognostic and therapeutic features. This type of breast cancer shows a higher rate of multiple metastases with a more frequent axillary-lymph-node involvement. Related to these dissemination and metastatic features, we aimed to study the immunohistochemical expression of D2-40, VEGF-C and VEGFR-3 in 25 cases of ILCs stratified according to the histopathological and molecular classification. Regardless of histopathological or molecular subtype, the statistical tests proved that for ILC, the highest D2-40 lymphatic microvessels density (LMVD) was in the peritumoral areas. In classical subtype, the LMVD values were positively correlated with the degree of tumor differentiation and pTNM clinical stages and when these cases were classified based on the molecular criteria the highest recorded values were found in the luminal B subtype. In addition, regardless of the histopathological and molecular subtypes, the D2-40 LMVD varied in the same direction for both VEGF-C and VEGFR-3 categories, with the highest LMVD values recorded in those cases with the highest VEGF-C and VEGFR-3 reactivity, especially in the peritumoral areas. Considering only the molecular luminal A and B subtypes, we have noted that VEGF-C and VEGFR-3 expression was significantly higher in luminal A subtype compared to luminal B. This immunoprofile suggests the existence of a tumor type-specific lymphangiogenesis that may have certain prognostic and therapeutic implications.

Expression of CXCR4, MMP-13 and ß-catenin in different histological subtypes of facial basal cell carcinoma.

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans, accounting for almost 80% of all non-melanoma skin cancers worldwide. The nodular and infiltrative-morpheaform are the most common BCC types in the head and neck region and together with the micronodular subtypes are the most aggressive tumors, because of their tendency to infiltrate the deep subcutis, muscles and even bones. To explain the local aggressive behavior and their metastatic potential, many studies have been performed to identify the molecular determinants implicated in BCC tumor progression. For this reason, we investigated the immunohistochemical expression of CXCR4, MMP-13 and ß-catenin expression in six metatypical, eight infiltrative-morpheaform, six micronodular and five superficial facial BCCs. For all three markers, the tumor reactivity varied with the histological type. The highest reactivity was observed in metatypical subtype, especially at the level of areas with squamous cells differentiation. The lowest reactivity was recorded in micronodular and superficial BCC subtypes. Regardless histological subtype, the tumor reactivity was higher at the advancing edge and additional a strong stromal reaction was noticed for all investigated markers peculiar in fibroblasts, inflammatory cells and endothelial cells. All these data proved the utility of CXCR4, MMP-13 and ß-catenin immunohistochemical investigation in BCCs both for identification of high-aggressive tumors and to develop novel more efficient therapeutic strategy for these patients by targeting these biomarkers.