HIV patient with pseudomyxoma peritonei of extra-appendiceal origin is disease-free and alive 9 years after complete cytoreductive surgery.

OBJECTIVE: Pseudomyxoma peritonei (PMP) is a clinical syndrome that is mainly characterized by the presence of mucinous ascites that results from the rupture of a mucin-producing neoplasm. No reports exist so far regarding the management of this syndrome in HIV patients. CASE REPORT: A 54-year old male patient with a diagnosed atypical colitis developed additionally over time a complicated diverticulitis which was initially treated conservatively with antibiotics. Due to septic complication, the patient received a Hartmann resection. Six months after the first surgery a Hartmann reversal was tried; it, however, revealed peritoneal implants and a significant stenosis of the colon stump. Resection of these lesions confirmed histopathologically the presence of a low-grade pseudomyxoma peritonei. Five months later, a second try for a Hartmann reversal was performed. In the view of the slightly enlarged paracolic lymph nodes, a low anterior resection was performed with a primary descendorectostomy. Histopathological examination revealed no more signs of the tumor, which confirmed the completeness of the cytoreductive surgery by the first try for a Hartmann reversal. CONCLUSIONS: Completeness of cytoreductive surgery and low grade histology seem to be the most important factors for the prognosis in pseudomyxoma peritonei in immunocompromised patients as suggested by the long overall and progression free survival of the present patient.

High Farnesoid X Receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma.

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells' proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients' survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma.

Elevated Farnesoid X Receptor (FXR) and Retinoid X Receptors (RXRs) expression is associated with less tumor aggressiveness and favourable prognosis in patients with pancreatic adenocarcinoma.

UNLABELLED: Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are considered to participate in crucial biochemical and cellular processes, being involved in the pathogenesis of several diseases, including cancer. The present study aimed to evaluate the clinical significance of FXR alone and in conjunction with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-α, -ß and -γ protein expression was assessed immunohistochemically on tumoral samples of 55 pancreatic adenocarcinoma cases and was statistically analyzed with clinicopathological characteristics, tumor proliferative capacity and patients' survival. Enhanced FXR expression was borderline associated with earlier histopathological stage (p=0.054). Concomitant elevated FXR/RXR-α expression was significantly associated with decreased tumor histological grade (p=0.017), while concomitant enhanced FXR/RXR-ß and FXR/RXR-γ expression with earlier histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-γ expression was additionally significantly associated with the absence of lymph node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR, FXR/RXR-ß or -γ expression showed significantly longer survival times compared to those with low expression (p=0.013, p=0.021 and p<0.001, respectively). In multivariate analysis, FXR and FXR/RXR-γ expression were identified as independent prognostic factors (p=0.044 and p=0.001, respectively). CONCLUSION: The present study suggested that FXR and RXRs were implicated in pancreatic malignant disease progression, reinforcing their utility as clinical markers for patients' management and prognosis, as well as targets for potential therapeutic interventions. KEYWORDS: FXR, RXR, pancreatic adenocarcinoma, immunohistochemistry, clinicopathological parameters, patients' survival.

Entropy measures for discrimination of 'awake' Vs 'anaesthetized' state in recovery from general anesthesia.

Approximate Entropy (ApEn) and Permutation Entropy (PE) have been recently introduced for assessment of anesthetic depth. Both measures have previously been shown to track changes in the electrical brain activity related to the administration of anesthetic agents. In this paper ApEn and PE are compared for the automatic classification of 'awake' and 'anesthetized' state using a Support Vector Machine to assess their robustness for potential use in a device for monitoring awareness during general anesthesia. It was found that both measures provide linearly separable features and we are able to discriminate between the two states with accuracy greater than 96% using either of the two entropy measures.

Pure vulvar Langerhans cell histiocytosis: a case report and literature review.

Langerhans cell histiocytosis (LCH) of the female genital tract is a very rare disease. Only 16 cases of primary vulvar LCH without subsequent systemic spread of disease have previously been published in the literature. We describe an additional case of LCH in which the lesion was confined to the vulva. A 52-year-old Caucasian woman presented for further investigation with a 6-month history of vulvar pruritus. Physical examination revealed multiple fine red papules on both labia minor. A metastatic workup did not reveal any evidence of disease beyond the vulva. The lesion was biopsied, and histological findings were characteristic of LCH. The patient was treated by local extirpation of both labia minor. Ten months after surgery, the patient has no signs of local recurrence or systemic spread. It is necessary to perform a biopsy of the lesions when a woman presents atypical chronic lesions on the vulva. Although different treatment has been proposed, complete surgical excision is fundamental in "pure" genital Langerhans cell histiocytosis as initial therapy.

Poorly differentiated carcinoma of the rectum with aberrant immunophenotype: a case report.

We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intra-abdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen (EMA) immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen (LCA) were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase (NSA) was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity (100%) was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor (STI571) similar to that which has been proposed in GISTs.

Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression.

INTRODUCTION: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. METHODS: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. RESULTS: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001, p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall survival (p=0.031) of the patients. High LVD correlated with poor disease-free and overall survival only in the subgroup of patients with ER-negative tumors (p=0.056 and p=0.0312 respectively). CONCLUSION: These findings, for the first time, correlate lymphatic size with tumors of limited proliferative potential and higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D expression influence lymphatic size rather than being involved in the increase of lymphatic vessel number.

Metastatic low-grade endometrial stromal sarcoma of clitoris: report of a case.

Low-grade endometrial stromal sarcoma (ESS) is an uncommon neoplasm, which has a highly recurrent nature. A review of the literature revealed that only one case of low-grade ESS, arising within the vulva from a focus of endometriosis, has been previously published. We describe an additional case of low-grade ESS arising within the vulva and to the best of our knowledge the first report of low-grade ESS metastasized to clitoris. A 46-year-old woman was admitted to our hospital due to a heavy uterine bleeding. A physical examination revealed a lesion in clitoris, which exhibited a densely cellular mesenchymal neoplasm on microscopy. On the basis of the pathologic features alone, a differential diagnosis of a low-grade ESS and cellular leiomyoma was considered. Seven months later, the patient presented again with excessive uterine bleeding and a total hysterectomy was performed. A tumor of white-tan, whorled appearance was found. Its features were suggestive of low-grade ESS. Taking into account the possible extrauterine location of an ESS and reviewing the first case, a diagnosis of rare low-grade ESS metastasized to clitoris was made.

Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma.

AIMS: Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma. MATERIAL AND METHODS: Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed. RESULTS: VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively). CONCLUSION: VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.

Effect of different ERK2 protein localizations on prognosis of patients with invasive breast carcinoma.

Mitogen-activated protein kinase (MAP kinase) pathways represent a cascade of phosphorylation events, including three pivotal kinases, Raf, MEK and ERK1/2, which have been implicated in the pathogenesis of cancer. We examined 151 cases of invasive breast carcinoma by immunohistochemistry and compared the ERK2 expression with clinicopathological parameters, MMP-11 immunoexpression and patients' survival. ERK2 immunoexpression was detected in the cytoplasm and nucleus of cancer cells in 37.7% and 19.2% of cases, respectively. Nuclear ERK2 was inversely correlated with ER (p = 0.039), whereas cytoplasmic ERK2 was positively correlated with MMP-11 in fibroblasts (p = 0.032) and more often expressed in lobular than ductal carcinomas (p = 0.026). Nuclear ERK2 expression was found to be an independent prognostic factor of shortened overall survival of patients (p = 0.040), while cytoplasmic ERK2 had an independent, favorable effect on both disease-free and overall survival (p < 0.0001 and p = 0.002, respectively). These findings suggest that the different subcellular localizations of ERK2 seem to be related to different, possibly contradictory, effects on patient survival.

The favorable prognostic impact of tissue inhibitor of matrix metalloproteinases-1 protein overexpression in breast cancer cells.

The tissue inhibitor of metalloproteinases-1 (TIMP1) inhibits tumor cell invasion and metastasis in experimental models; in addition, TIMP1 is supposed to possess another important function, cell growth promotion. The potential prognostic significance of TIMP1 in breast cancer remains unclear. We evaluated the significance of the immunohistochemical expression of TIMP1 in a well-documented series of 133 infiltrating breast carcinomas by examining any possible statistical association between this expression and numerous clinicopathological parameters as well as patients' disease-free interval. TIMP1 was generally expressed in both stromal and cancer cells in our specimens. TIMP1 was overexpressed in cancer cells of 60.15% of all cases. Tumors of high histological and nuclear grade were found to overexpress TIMP1 less frequently than the rest (p=0.003 and p=0.057, respectively). Interestingly, TIMP1 overexpression was inversely associated with cell proliferation, the latter being evidenced by Ki67 immunoreactivity (p=0.028). TIMP1 immunostaining was in parallel with metalloproteinase-2 (MMP2) immunoexpression in both cancer and stromal cells. Multivariate analysis disclosed that TIMP1 overexpression in cancer cells was an independent determining factor for prognosis (p=0.006); TIMP1 overexpression in malignant cells appeared to correlate with favorable outcome, particularly in patients with lack of nodal metastases and in patients with MMP2-negative immunophenotype (p=0.0252). The upregulation of TIMP1 cancer cell expression in breast cancer may suggest that this marker has a multifunctional role apart from that of metalloproteinase inhibitor since it was found to be related to malignant cells' differentiation and proliferation. TIMP1 overexpression in cancer cells appears for the first time to be a promising indicator of favorable prognosis in breast cancer.

Immunohistochemical expression of caspase-3 as an adverse indicator of the clinical outcome in human breast cancer.

OBJECTIVE: Tumor growth is the net result of cell proliferation and cell loss by apoptosis. Caspase-3 (CPP32) has been considered as most directly correlated with apoptosis because of its location in the protease cascade pathway. The aim of this study was to examine the relation of the immunohistochemical expression of caspase-3 in 137 infiltrating breast carcinomas to patients' clinicopathological parameters and survival. METHOD: A polyclonal antibody against caspase-3 was applied using a standard immunohistochemical procedure to paraffin sections. RESULTS: By comparison with nonneoplastic breast tissue, caspase-3 appeared to be upregulated in malignant breast tissue, and its overexpression status was detected in 75.2% of the specimens. Significant statistical correlations were observed between overexpression of caspase-3 and low nuclear grade (p = 0.048), lack of p53 protein accumulation (p = 0.039), bcl-2-positive immunostaining (p = 0.027), as well as tissue inhibitor of metalloproteinase-2 immunoreactivity of neoplastic (p = 0.012) and stromal cells (p = 0.0001). Despite the above correlations, multivariate analysis revealed a significant negative influence of caspase-3 expression on patients' overall survival (p = 0.029). CONCLUSIONS: Caspase-3 protein overexpression appears to be involved in the apoptotic pathways influenced by wild-type p53 and bcl-2 proteins. Moreover, the results show that caspase-3 overexpression in breast cancer cells seems to exert an independent adverse effect on patients' overall survival.

DNA topoisomerase II-alpha immunoreactivity as a marker of tumor aggressiveness in invasive breast cancer.

OBJECTIVE: The nuclear enzyme DNA topoisomerase (topo) II breaks and rejoins DNA strands; its isoform topo IIalpha is associated with active cell proliferation of mammalian cells. The aim of this study was to examine the relationship between the expression of topo IIalpha and biological behavior markers in breast cancer. METHODS: Formalin-fixed, paraffin-embedded tissue from 88 samples of infiltrating breast cancer was immunohistochemically stained for topo IIalpha. For each case, a topo IIalpha index was determined by image analysis. Similar indexes were available for Ki-67 protein, a known cell proliferation marker, and p53, bcl-2 and c-erbB-2 oncoproteins. Each case had been staged and graded and the patients had been followed up for a mean period of 61.62 months. RESULTS: Elevated topo IIalpha immunopositivity (in >10% of malignant nuclei) was detected in 22 tumors, and this immunostatus was statistically associated with poor nuclear differentiation, absence of steroid hormone receptors, high Ki-67 immunoexpression, p53 protein accumulation and c-erbB-2 protein overexpression. Topo IIalpha expression was not linked with disease extent (stage or lymph node status). Neither proliferation marker (topo IIalpha or Ki-67) had any significant influence on the patients' recurrence-free survival. CONCLUSION: From the above results, we conclude that topo IIalpha overexpression appears to be linked with cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer.