KISS1/KISS1R expression in eutopic and ectopic endometrium of women suffering from endometriosis.

BACKGROUND: The KISS1/KISS1R system has been implicated in the physiology of reproduction and many studies have documented the stimulatory effect of kisspeptin on Gonadotropin-releasing Hormone (GnRH) and gonadotropin secretion. In addition, the KISS1/KISS1R system has been implicated in several pathophysiological processes, including cancer. MATERIALS AND METHODS: We examined the pattern of KISS1 and KISS1R expression in eutopic and ectopic endometrium tissues which were obtained from 24 women suffering from endometriosis and 16 control women who underwent laparoscopic excision for other benign gynecological diseases. RESULTS: Significant KISS1R expression was detected in 10 out of the 24 samples of eutopic endometrial biopsies of women suffering from endometriosis, while their matched biopsies of ectopic endometrial lesions did not reveal any KISS1R expression. KISS1R expression was not detected in the endometrial biopsies of control women. In addition, KISS1 expression was not detected in practically any the endometrial tissues of either control women or women with endometriosis. CONCLUSION: The expression of KISS1R in 10/24 samples of human endometrial biopsies of women suffering from endometriosis and the loss of its expression in the samples of matched ectopic endometrial tissues, suggests that the KISS1/KISS1R system may play a role in the pathophysiology of endometriosis only for a particular group of patients. Since KISS1 is not expressed by the endometrium and endometriotic tissue, it is conceivable that the activation of KISS1R in this particular group is mediated by KISS1 expression by non-endometrial tissues (endocrine action).

Nasal inflammation in sleep apnoea patients using CPAP and effect of heated humidification.

Nasal continuous positive airway pressure (CPAP) can cause undesirable nasal symptoms, such as congestion to obstructive sleep apnoea (OSA) patients, whose symptoms can be attenuated by the addition of heated humidification. However, neither the nature of nasal symptoms nor the effect of heated humidification on nasal pathophysiology and pathology are convincingly known. 20 patients with OSA on nasal CPAP who exhibited symptomatic nasal obstruction were randomised to receive either 3 weeks of CPAP treatment with heated humidification or 3 weeks of CPAP treatment with sham-heated humidification, followed by 3 weeks of the opposite treatment, respectively. Nasal symptom score, nasal resistance, nasal lavage interleukin-6, interleukin-12 and tumour necrosis factor-α and nasal mucosa histopathology were assessed at baseline and after each treatment arm. Heated humidification in comparison with sham-heated humidification was associated with decrease in nasal symptomatology, resistance and lavage cytokines, and attenuation of inflammatory cell infiltration and fibrosis of the nasal mucosa. In conclusion, nasal obstruction of OSA patients on CPAP treatment is inflammatory in origin and the addition of heated humidification decreases nasal resistance and mucosal inflammation.

The clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 according to their localization in invasive breast carcinoma.

AIMS: To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c-erbB2 and peroxisome proliferator-activated receptor (PPAR) gamma. METHODS: Immunohistochemistry was carried out on 175 paraffin-embedded breast tissue specimens to detect MT1-MMP, MMP-9, oestrogen receptor (ER), progesterone receptor, c-erbB-2, Ki67, topoisomerase IIalpha (topo IIalpha) and PPARgamma protein expression. RESULTS: Both MT1-MMP and MMP-9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1-MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIalpha (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1-MMP was positively associated with MMP-9 (P = 0.010) and PPARgamma (P < 0.0001). Cytoplasmic MMP-9 was inversely associated with Ki67 (P = 0.034) and topo IIalpha (P = 0.004), whereas its relationship with MT1-MMP (P = 0.034) and PPARgamma (P = 0.024) was found to be positive. Stromal MMP-9 was more often observed in c-erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse-free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). CONCLUSIONS: Cytoplasmic MT1-MMP and MMP-9 seem to be related to well-differentiated tumours, with a low proliferation potential, while stromal MMP-9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.

An immunohistochemical evaluation of phosphorylated Akt at threonine 308 [pAkt(Thr308)] in invasive breast cancer.

BACKGROUND: Akt is a serine/threonine kinase which is fully activated when phosphorylated (pAkt). The aim of this study was to investigate the expression pattern of phosphorylated Akt at Threonine 308 [pAkt(Thr308)] in association with clinicopathological parameters and various biological markers. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 152 invasive breast carcinomas to detect the expression of the proteins pAkt(Thr308), estrogen (ER) and progesterone (PR) receptors, p53, Ki-67 and c-erbB-2. RESULTS: pAkt(Thr308) protein was immunodetected in the cytoplasm and the nuclei of the malignant cells. pAkt was found to be positively associated with the lobular histological type, while it was found to exert no impact on patients' survival. pAkt(Thr308) immunopositivity was inversely related to Ki-67 and p53 (p=0.013 and p=0.020, respectively), while being positively associated with cerbB2 expression (p=0.005). CONCLUSION: This is the first study to show a frequent detection of pAkt(Thr308) in lobular breast carcinomas and an association of its expression with indices of proliferation (c-erbB2, Ki-67) and apoptosis (p53).

Protective role of oral antioxidant supplementation in ocular surface of diabetic patients.

AIM: To investigate the effect of vitamin C and E supplementation in the levels of nitrite, nitric oxide (NO) related metabolite, and ocular surface parameters in diabetic patients. METHODS: 50 patients with non-insulin dependent diabetes mellitus were given vitamin C (1000 mg/day) and vitamin E (400 IU/day) supplementation for 10 days. Nitrite levels in tears were measured by photometric determination before and after vitamin supplementation. Tear function parameters (Schirmer test I, BUT, ocular ferning test) and brush cytology analysis of the conjunctival epithelium were also evaluated. RESULTS: Nitrite levels were found to be significantly reduced (p<0.05) after 10 days of vitamin C and E supplementation. Improved values for Schirmer test, BUT test, and ocular ferning test were also found. Goblet cell density and grading of squamous metaplasia showed a significant improvement. CONCLUSIONS: Oxidative stress and free radical production are elevated in diabetes mellitus. Antioxidants, such as vitamin C and vitamin E, probably have an important role in reducing the oxidative damage produced by nitric oxide and other free radicals and improving the ocular surface milieu.

Unusual sclerosing haemangiomas and sclerosing haemangioma-like lesions, and the value of TTF-1 in making the diagnosis.

AIMS: Sclerosing haemangiomas typically comprise a mixture of four architectural patterns (papillary, sclerotic, solid and haemorrhagic) and two cell types, eosinophilic cuboidal epithelial lining cells and sheets of rounded cells with either eosinophilic or clear cytoplasm. In most instances, recognition of these architectural and cytological features provides sufficient evidence for diagnosis. This study presents and discusses the histogenesis of four cases where difficulties in diagnosis were encountered, and reports the value of the antibody TTF-1 in making the diagnosis. METHODS AND RESULTS: Four cases with focal areas reminiscent of sclerosing haemangioma were reviewed and immunostained with an antibody panel including antibodies to TTF-1 and surfactant apoprotein A. Of these, one case was classified as sclerosing haemangioma combined with typical carcinoid, in which there was a mediastinal lymph node metastasis solely comprising the solid component of sclerosing haemangioma. The second was classified as an alveolar adenoma with sclerosing haemangioma-like areas. In the remaining two cases, diagnosis was confounded by presentation with predominantly cystic masses, the largest 70 mm in diameter. Immunohistochemically, TTF-1 was of greater value than surfactant apoprotein, in particular in identifying the solid component of sclerosing haemangioma when this was solely present. CONCLUSION: Sclerosing haemangiomas should be considered in the differential diagnosis of cystic pulmonary masses. They may also present histologically as combined tumours and metastasize to mediastinal nodes, indicating an, albeit low, malignant potential. TTF-1 is a valuable antibody in identifying the presence of a sclerosing haemangioma when typical features are absent.