Tiam1 Protein Expression in Primary and Metastatic Colorectal Carcinoma: A Retrospective Study of 200 Cases

Objective: T-cell Lymphoma Invasion and Metastasis 1 (Tiam1)protein is a guanine nucleotide exchange factor that activates proteins of the Rho family of GTPases, specifically Rac1. Expression of Tiam1 protein has been reported in various human cancers and has been associated with lymphangiogenesis and promotion of tumor metastasis. The objective of this study was to further evaluate the expression of Tiam1 in primary and metastatic colorectal cancer (CRC) and its association withvariousclinicopathological parameters, includinggender, age, tumor size, Dukes stage, tumor grade, lymph node status and original location of the primary tumor (colon versus rectum).Methods: The expression of Tiam1 was detected by immunohistochemistry in 200 samples of primary CRC tissues and in 100 samples of lymph node tissue with CRC metastases.Results: Tiam1 was overexpressed in the majority of both primary (69,5% of the cases) and metastatic (63% of the cases) CRC tumor tissues. Overexpression of Tiam1 in primary CRC was statistically associated withlowertumor grade(P=0,04), whereas in metastatic CRC a statistically significant association between Tiam1 expression and  female gender (P=0,003), tumor size 5cm (P=0,001) and localization  of the primary tumor in the colon (P=0,009) was found.Conclusion: Overexpression of Tiam1 protein may represent a frequent event in CRC. Additional studies are warranted to further investigate its potential value as a marker of prognosis and treatment response in this form of cancer

Immunocytochemical detection of apoptotic markers in smears from precancerous and cancerous lesions of the uterine cervix: correlation with HPV infection and cytomorphologic findings in conventional and ThinPrep cervical samples

In the present study, cervical smears from women with intraepithelial lesionsand with normal cytology were analyzed morphologically and with the use of immunocytochemical methods. The aim of our morphologic study was to reevaluate the reproducibility of the automated processing of the cervical samples collected with the ThinPrep (TP) method, and to further investigate the potential diagnostic value of additional slides prepared from residual TP Pap Tests. Our results suggest that repeat processing of residual cervical TP samples may not be an invariably reproducible procedure and the first slide may not be necessarily representative of the specimen as a whole. An additional finding of our study is that an upgrading of the cytological diagnosis after repeat processing is more likely to occur in cases initially classified as “ASC-US” or as “squamous intraepitheliallesion, grade cannot be determined” than in cases with an initial negative or HSIL diagnosis. The aim of our immunocytochemical study was to detect the expression pattern of p53, PTEN, Fas, p16 and L1 proteins in intraepithelial lesions and to investigate their potential correlations to each other as well as their value asprognostic markers in LSIL cases. Our results suggest the following : a) loss of PTEN or Fas expression and p53 overexpression may be independently involved, even as early events, in the process of neoplastic transformation of the cervical epithelium by facilitating transition to higher grade dysplasia b)a strong nuclear and cytoplasmic immunocytochemical expression pattern ofp16 might be a strong indicator for the presence of a high grade lesion, and could serve as a useful diagnostic adjunct especially in the presence of equivocal cytomorphologic findings and c) the combined immunocytochemical expression pattern of p16 and L1 proteins may also confer significant diagnostic information as regards the determination of lesion grade and probably contribute in the identification of women at greater risk for developing invasive carcinoma, even when the HPV status is unknown. The potential prognostic value of our examined markers in LSIL cases was not verified in our study and should be further evaluated in future large prospective series.Στην παρούσα μελέτη μελετήθηκαν τόσο μορφολογικά όσο και με ανοσοκυτταροχημικές μεθόδους τραχηλικά επιχρίσματα κατά Παπανικολάου από γυναίκες με ενδοεπιθηλιακές αλλοιώσεις του τραχήλου της μήτρας και με φυσιολογικά ευρήματα. Σκοπός της μορφολογικής μας μελέτης ήταν η επαναξιολόγηση της αναπαραγωγιμότητας της τεχνικής επεξεργασίας των τραχηλικών δειγμάτων υγρής φάσης ThinPrep καθώς και της πιθανής διαγνωστικής αξίας της μεθόδου παρασκευής επιπρόσθετων πλακιδίων εκ του υπολειπόμενου υλικού. Τα αποτελέσματά μας έδειξαν ότι η επαναλαμβανόμενη επεξεργασία των τραχηλικών δειγμάτων ΤΡ μπορεί να μην είναι πάντα και ανεξαιρέτως μια αναπαραγώγιμη διαδικασία και το αρχικό πλακίδιο που παρασκευάζεται μπορεί να μην είναι σε κάθε περίπτωση αντιπροσωπευτικό του συνόλου του δείγματος.Η μελέτη μας κατέδειξε επίσης ότι η πιθανότητα αναθεώρησης της αρχικής διάγνωσης μετά την αξιολόγηση των επαναληπτικών πλακιδίων ThinPrep είναι σημαντικά μεγαλύτερη σε αμφιλεγόμενα περιστατικά, όπως οι περιπτώσεις ASCUS(atypical squamous cells of undetermined significance/ άτυπα πλακώδηκύτταρα αδιευκρίνιστης σημασίας) ή οι δύσκολες διαγνωστικά περιπτώσεις με στοιχεία χαμηλού βαθμού δυσπλασίας στις οποίες δεν μπορεί με βεβαιότητα να αποκλειστεί και η πιθανότητα υψηλόβαθμης αλλοίωσης.Σκοπός της ανοσοκυτταροχημικής μας μελέτης ήταν η διερεύνηση της συχνότητας και του προτύπου πιθανής διαταραχής της έκφρασης των πρωτεϊνώνp53, PTEN, Fas, p16 και L1 στις ενδοεπιθηλιακές αλλοιώσεις του τραχήλου της μήτρας, των πιθανών αλληλοεπιδράσεων των δεικτών αυτών μεταξύ τους καθώς και της πιθανής αξίας της ανοσοκυτταροχημικής τους έκφρασης ως δεικτών πρόγνωσης στις χαμηλού βαθμού δυσπλασίες. Τα αποτελέσματά μας έδειξαν : α)ότι η διαταραχή της έκφρασης των πρωτεϊνών p53, PTEN, και Fas μπορεί να παρατηρηθεί ακόμη και στο ενδοεπιθηλιακό στάδιο της καρκινογένεσης στον τράχηλο της μήτρας, και ενδέχεται να διευκολύνει τη μετάβαση από τη χαμηλού βαθμού στην υψηλού βαθμού δυσπλασία β)ότι η ανοσοκυτταροχημική κατάδειξη της υπερέκφρασης της πρωτεϊνης p16 σε τραχηλικά επιχρίσματα, ειδικά όταν αυτή είναι έντονη και εντοπίζεται τόσο στον πυρήνα όσο και στο κυτταρόπλασμα του κυττάρου, μπορεί να αποτελεί ένα χρήσιμο διαγνωστικό δείκτη για την τεκμηρίωση της παρουσίας υψηλού βαθμού (αντί για χαμηλού βαθμού) ενδοεπιθηλιακής αλλοίωσης, ιδιαιτέρως στις περιπτώσεις με αμφιλεγόμενα κυτταρομορφολογικά ευρήματα και γ) ότι η συνδυασμένη ανοσοκυτταροχημική χρώση για τις πρωτεϊνες p16 και L1 μπορεί επίσης να συμβάλλει στη διάκριση των χαμηλόβαθμων από τις υψηλόβαθμες αλλοιώσεις,και στην αναγνώριση των γυναικών υψηλού κινδύνου για την ανάπτυξη διηθητικής νόσου, ακόμη και σε περιπτώσεις με άγνωστο HPV status. Η πιθανή αξία των πρωτεϊνών που μελετήσαμε ως δεικτών πρόγνωσης των χαμηλού βαθμού ενδοεπιθηλιακών αλλοιώσεων δεν επιβεβαιώθηκε στο υλικό της παρούσας εργασίας

Bone marrow micrometastases in different solid tumors: Pathogenesis and importance

Early dissemination of cancer cells from the primary tumor via the circulatory system may result in the formation of microscopic metastatic deposits (micrometastases, MMs) in secondary compartments such as the bone marrow (BM), where there is a favorable environment for their subsequent growth and spread. MMs are considered the main reason for metastatic relapse in patients with early stage solid cancers after resection of the primary tumor. Although the molecular pathways leading to MMs remain only partly understood, there is increasing evidence that the detection of MMs in BM aspirates at the time of primary diagnosis is an independent prognostic factor, with a major influence in the stratification of these patients for adjuvant clinical treatment. Further potential applications of the detection of MMs include their use in monitoring therapeutic response or even in revealing targets for novel systemic therapies. All these intriguing possibilities are intensely investigated and carry great promise for radical improvements in the assessment and treatment of several epithelial. cancers which are currently to blame for the majority of cancer-related deaths in the industrialized world. (C) 2008 Elsevier Ltd. All rights reserved

Bevacizumab in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for first-line and maintenance treatment of metastatic colorectal cancer

Despite a slight decrease in mortality rates, recent advances in screening methods, diagnosis and overall improved therapeutic options, colorectal cancer (CRC) remains among the leading causes of cancer-related death worldwide. The major cause is the mortality related to metastatic status of CRC. Increasing clinical evidence derived from randomized trials strongly suggests that the efficacy of standard cytotoxic agents, including various combinations of 5-fluoouracil (5-FU)/leucovorin (LV), capecitabine, irinotecan and oxaliplatin, may be significantly augmented with concomitant administration of molecular agents targeting the vascular endothelial growth factor (VEGF) signaling pathways, such as bevacizumab. Herein, we critically discuss the current data on the efficacy and safety profile of bevacizumab in combination with fluoropyrimidine-based chemotherapy for first-line and maintenance treatment of metastatic CRC and briefly comment on existing controversies and future perspectives

Targeted therapies for pancreatic adenocarcinoma: Where do we stand, how far can we go?

Pancreatic adenocarcinoma (usually referred to as pancreatic cancer) is a highly lethal and aggressive malignancy with a disease-related mortality almost equaling its incidence, and one of the most challenging cancers to treat. The notorious resistance of pancreatic cancer not only to conventional cytotoxic therapies but also to almost all targeted agents developed to date, continues to puzzle the oncological community and represents one of the biggest hurdles to reducing the death toll from this ominous disease. This editorial highlights the most important recent advances in preclinical and clinical research, with regards to targeted therapeutics for pancreatic cancer, outlines current challenges and provides an overview of potential future perspectives in this rapidly evolving field

Acute Generalized Exanthematous Pustulosis Induced by Amoxicillin/Clavulanic Acid: Report of a Case Presenting With Generalized Lymphadenopathy

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously