Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated

Clinical significance of RCAS1 expression in thyroid cancer

The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that contributes to tumor progression by enabling cancer cells to evade immune surveillance. The present study aimed to evaluate the clinical significance of RCAS1 expression in human benign and malignant thyroid lesions.RCAS1 protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 121 patients with benign and malignant lesions and was associated with type of thyroid histopathology and tumor stage parameters such as tumor size, lymph node metastases, capsular, lymphatic and vascular invasion.RCAS1 positivity, overexpression and staining intensity provided a distinct discrimination between benign and malignant thyroid cases (p=0.0006, p=0.0001 and p=0.0001, respectively), as well as between hyperplastic nodule and papillary carcinoma cases (p=0.0229, p=0.0001 and p=0.0001, respectively). RCAS1 positivity, overexpression and staining intensity also provided distinct discrimination between cases with Hashimoto thyroiditis and those with hyperplastic nodule (p=0.0221, p=0.0001 and p=0.0019, respectively). In the subgroup of malignant thyroid lesions, RCAS1 overexpression was significantly associated with large tumor size (p=0.0246), the presence of lymph node metastases (p=0.0351) and capsular invasion (p=0.0397).RCAS1 protein may participate in thyroid neoplastic transformation and could be considered as a useful biomarker to improve diagnostic scrutinyΤο RCAS1 (Receptor-Binding Cancer Antigen expressed on SiSo cells) είναι ένα αντιγόνο συσχετιζόμενο με τον καρκίνο και είναι ένα μοναδικό μόριο που συμβάλλει στην ανάπτυξη καρκινικών όγκων με πολλαπλούς τρόπους. Επάγει την απόπτωση και διακόπτει την ανάπτυξη των κύτταρων που εμφανίζουν υποδοχείς του RCAS1. Μεταξύ αυτών των κυττάρων περιλαμβάνονται τα ενεργοποιημένα T-λεμφοκύτταρα και τα NK κύτταρα. Έτσι το RCAS1 φαίνεται να είναι υπεύθυνο για την ικανότητα των καρκινικών κύτταρων να διαφεύγουν της ανοσοεπιτήρησης του ξενιστή, και της δημιουργίας ανοχής στα καρκινικά κύτταρα από τον ξενιστή. Ακόμα το RCAS1 σχετίζεται με την ανάπτυξη του όγκου και την απόκτηση κακοήθων χαρακτηριστικών από τον όγκο, όχι μόνο επάγοντας την απόπτωση των λεμφοκυττάρων, αλλά και μέσω της αναδιαμόρφωσης του εξωκυτταρίου στρώματος του μικροπεριβάλλοντος του όγκου. Έτσι διευκολύνεται η τοπική και την απομακρυσμένη διασπορά του όγκου.Στην παρούσα μελέτη η έκφραση του RCAS1 μελετήθηκε ανοσοϊστοχημικά σε 121 κύβους παραφίνης, ασθενών που είχαν υποβληθεί σε ολική θυρεοειδεκτομή τόσο για καλοήθεις όσο και για κακοήθεις παθήσεις.Παρουσιάστηκε στατιστικά σημαντική διαφορά στην θετική ανοσοαντίδραση, υπερέκφραση αλλά και ένταση της χρώσης του RCAS1 μεταξύ των καλοήθων και κακοήθων παθήσεων του θυρεοειδούς (p=0.0006, p=0.0001 και p=0.0001 αντίστοιχα), αλλά και μεταξύ του θηλώδους καρκίνου και των υπερπλαστικών όζων του θυρεοειδούς (p=0.0229, p=0.0001 και p=0.0001 αντίστοιχα). Το ίδιο συνέβη και μεταξύ της θυρεοειδίτιδας Hashimoto και των υπερπλαστικών όζων (p=0.0221, p=0.0001 και p=0.0019 αντίστοιχα). Στην ομάδα των ασθενών με καρκίνο θυρεοειδούς αδένα η υπερέκφραση του RCAS1 σχετίστηκε με το μέγεθος του όγκου, (p=0.0246) την ύπαρξη λεμφαδενικών μεταστάσεων (p=0.0351) και την διήθηση της κάψας του θυρεοειδούς (p=0.0397).Το RCAS1 φαίνεται να λαμβάνει μέρος στην καρκινογένεση του θυρεοειδούς και μπορεί να χρησιμοποιηθεί ως βιοδείκτης για την διάγνωση του θυρεοειδικού καρκίνου

Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance

The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients

Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance

The 7th TNM classification clearly states that micro-metastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage.. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients. (C) 2012 Baishideng. All rights reserved

Neutrophils to lymphocytes ratio as a useful prognosticator for stage II colorectal cancer patients

Abstract Background The incidence of colorectal cancer (CRC) is expected to increase by 80% in year 2035. Even though advantages in treatment of CRC have being made over the last decades, the outcome remains poor. Recently, several inflammatory markers including pretreatment neutrophil to lymphocyte ratio (NLR), have being used as prognostic factors, since host inflammatory response to cancer is believed to determine disease progression. The aim of this study is to evaluate the prognostic significance of pretreatment NLR, in terms of overall survival (OS), 5-year survival, disease-free survival (DFS) and recurrence, in CRC patients who underwent curative resection. Methods We retrospectively reviewed 296 patients, who were submitted to elective surgery as first therapeutic option in curative intent, between January 2010 and December 2015. Pretreatment NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS, 5-year survival, DFS and recurrence. Results The cutoff point of NLR was calculated with Kaplan-Meier curves and log-rank test to 4.7. Univariate and multivariate analyses disclosed elevated NLR as a significant dismal prognostic factor for DFS (HR 1.88; 95% CI 1.01–3.52; p = 0.048), 5-year survival (HR 2.14; 95% CI 1.12–4.10; p = 0.021) and OS (HR 2.11; 95% CI 1.11–4.03; p = 0.023). In a subgroup analysis, in patients with stage II CRC, NLR > 4.7 was a stronger poor predictor for DFS (HR 2.76; 95% CI 1.07–7.13; p = 0.036), 5-year survival (HR 3.84; 95% CI 1.39–10.63; p = 0.01) and OS (HR 3.62; 95% CI 1.33–4.82; p = 0.012). After adjusting stage for gender, age, location of the primary tumor, differentiation, as well as the presence of perineural, vascular, and lymphovascular invasion, the significance of NLR > 4.7 became more prominent for DFS (HR 2.85; 95% CI 1.21–6.73; p = 0.0176), 5-year survival (HR 4.06; 95% CI 1.66–9.93; p = 0.002) and OS (HR 4.07; 95% CI 1.69–9.91; p = 0.002) in stage II patients. Conclusion Pretreatment NLR > 4.7 is a poor prognostic factor for DFS, 5-year survival and OS in CRC patients undergoing curative resection. The dismal prognostic effect of NRL is magnified in Stage II CRC patients

Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene

Abstract The incidence of adrenal involvement in MEN1 syndrome has been reported between 9 and 45%, while the incidence of adrenocortical carcinoma (ACC) in MEN1 patients has been reported between 2.6 and 6%. In the literature data only unilateral development of ACCs in MEN1 patients has been reported. We report a 31 years-old female MEN1-patient, in whom hyperplasia of the parathyroid glands, prolactinoma, non functioning pancreatic endocrine carcinoma and functioning bilateral adrenal carcinomas were diagnosed. Interestingly, a not previously described in the literature data, novel germline mutation (p.E45V) in exon 2 of MEN1 gene, was detected. The association of exon 2 mutation of the MEN1 gene with bilateral adrenal carcinomas in MEN1 syndrome, should be further investigated.</p