Luca Reggiani-Bonetti

Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in stage I colorectal carcinoma

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to behave like a negative prognostic marker in stage I colorectal carcinoma. In the aim of clarifying whether its association with adverse outcome may descend from NGALs ability to regulate matrix metallo-proteinase-9 (MMP-9), we analyzed the correlation, prognostic value, and association with neo-angiogenesis of NGAL and MMP-9 immunohistochemical expression in a series of stage I colorectal carcinomas. A variable NGAL immunoexpression was demonstrated in 17 of the 48 analyzed cases with a significantly higher frequency of positive cases among patients showing disease progression. NGAL expression was also positively correlated with VEGF expression detected in the same cases. MMP-9 immunostaining was present in the cytoplasm of the neoplastic cells in 30 cases; no significant correlations were evidenced with NGAL expression, as well as with the various clinico-pathological parameters or with progression of the colorectal carcinomas. By contrast, NGAL expression was confirmed as a significant independent negative prognostic marker related to a shorter disease-free survival in stage I colorectal carcinoma. Our preliminary results suggest that the association of NGAL with poor outcome might be independent from MMP-9 regulation, thus highlighting its prognostic value in this neoplasia. If our findings are confirmed in further analyses, NGAL assessment might be used in order to select those patients with a higher progression risk and to submit them to adjuvant therapies useful to prevent adverse outcome.

Lymphatic vessel density and its prognostic value in stage I colorectal carcinoma

Aims The assessment of lymphatic vessel density (LVD) has been suggested as a tool to determine the metastatic risk of neoplasias. On this premise, the authors aimed to verify whether progression risk of stage I colorectal cancer may be related to LVD. The authors also evaluated and correlated vascular endothelial growth factor (VEGF)-A expression with LVD revealed in the same cases in order to investigate its potential lymphangiogenic role in the early stage colorectal cancer. Methods LVD and VEGF immunoexpression were analysed and compared in series of 29 stage I surgically resected colorectal carcinomas obtained from patients showing disease progression and in a cohort of 23 stage I colorectal cancers from patients with no evidence of disease progression. The prognostic value of LVD and of VEGF expression on the progression-free survival to colorectal cancer was investigated. Results A high density of peritumoural lymphatics (P-LVD) was significantly associated with high VEGF expression and disease progression. Moreover, high P-LVD and high VEGF expression were significant negative prognostic parameters associated with a shorter disease-free interval in stage I colorectal cancer. Conclusions If our findings are further confirmed in other studies, the assessment of P-LVD on surgical specimens might be used as a tool to identify patients with stage I colorectal cancer at higher risk of progression in order to submit them to adjuvant therapies. Since P-LVD seems to show a VEGF-A mediated regulation in stage I colorectal cancer, therapies targeting this factor might be exploited to reduce lymphangiogenesis and the progression risk of this neoplasia.

Neutrophil gelatinase–associated lipocalin: a new prognostic marker in stage I colorectal carcinoma?

TNM stage I colorectal cancer is commonly characterized by a good prognosis, with 5-year survival of around 80% to 90%. Nonetheless, disease progression occurs in a percentage of cases, although the causes of an adverse clinical course still remain to be clarified. In the present study, we analyzed and compared the immunohistochemical expression of neutrophil gelatinase-associated lipocalin, an iron-binding protein, which is involved in colorectal cancer progression, in series a of 29 surgically resected colorectal carcinomas obtained from patients who died of the disease and in a cohort of 22 colorectal cancers from patients alive 5 years after the initial diagnosis. The prognostic value of neutrophil gelatinase-associated lipocalin expression on the overall survival to colorectal cancer was investigated. Variable neutrophil gelatinase-associated lipocalin immunoexpression was demonstrated in 23 of the 51 analyzed cases, with a significantly higher frequency of positive cases among patients who died of the disease. Moreover, neutrophil gelatinase-associated lipocalin expression appeared to be a significant independent negative prognostic marker related to shorter overall survival in stage I colorectal carcinoma. If our findings are confirmed in further analyses, neutrophil gelatinase-associated lipocalin assessment might be used to select patients with a higher risk of progression and to find adjuvant therapies for the prevention of adverse outcomes.

Incidence trend of malignant polyps through the data of a specialized colorectal cancer registry: clinical features and effect of screening

Abstract Objectives. The purposes of the study are to describe the incidence trend of malignant polyp of large bowel over a 25-year period in the District of Modena and to assess the effect of an organized colorectal cancer screening program. Material and methods. Through the data of a specialized colorectal cancer Registry, we evaluate the clinical and pathological features of the polyps. Trend analysis was assessed with the Joinpoint Regression Program. Results. A total of 172 patients with malignant polyps were diagnosed throughout the study (3.5% of 4.835 registered patients); their overall frequency during the registration period increased from zero cases in the initial years (1984–85) to 57 cases in the past 3 years (2006–2008). Crude incidence rate passed from 0.37 in 1986–89 to 10.2 in 2006. Joinpoint trend analysis of crude rates showed a significant increase of incidence during the study period, with percent of annual variation ranging between 38.6% (95% CI 12.5–70.7) and 7.3% (95% CI 2.6–12.1). During the screening period (2005–2008, the past 4 years of registration) there was a significant increase of sessile polyps (p < 0.001), while other clinical and morphological features, including the number of low- and high-risk malignant polyps, remained unchanged. The surgery (after polypectomy) tended to raise both in low- and high-risk subgroups. Conclusion. The incidence of malignant polyps increased significantly from the initial to the most recent periods of colorectal cancer registration. Screening was associated with changes in gross morphology of polyps and with an increased use of the surgery after endoscopic polypectomy.

Hyperplastic and Inflammatory Pathology of the Thymus

Thymic hyperplasia describes a nonneoplastic condition of the thymus, characterized by an increased number of the constituent cells of the organ. This concept was initially introduced by Castleman in the late 1940s to define the thymic changes seen in association with myasthenia gravis [1]. Years later, Rosai and Levine [2] in the A.F.I.P. fascicle on “Tumors of the thymus” identified two distinct types of thymic hyperplasia on the basis of histopathologic criteria: true thymic hyperplasia, defined by an increase in the size and weight of the organ that retains a normal microscopic morphology, and lymphoid (or follicular) hyperplasia, characterized by the presence of lymphoid follicles with active germinal centers in the thymic medulla. In the last case, the size and weight of the thymus can be increased, but in most instances they are within normal limits. The term thymitis (or autoimmune thymitis), originally coined by Goldstein in 1966 [3], has been used interchangeably by some authors to denote the lymphoid hyperplasia of the thymus, since its morphological features, both at the light and electron microscopic levels, are markedly similar to those observed in any chronic inflammatory process of other organs [4, 5], being characterized by the presence of peripheral B lymphocytes, lymphoid follicles, and diffuse plasmacytosis.

Erratum to: Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a population-based study

Although surgery alone represents a curative approach for patients with pT3N0M0 colon cancer, about 15–20 % of these patients develop a relapse of disease. Microsatellite instability (MSI) is one of the most important molecular markers in colorectal cancer. The aim of this study was to investigate the prognostic relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the Province of Modena—(Northern Italy) within the 2002–2006 period in patients who showed a relapse of disease during the 5-year period of follow-up (59 cases). They were compared to 59 controls similar in clinical and pathological features but with good prognosis. 32 patients of the 118 cases received adjuvant chemotherapy, 16 (27 %) in the group of relapses and 16 (27 %) in the controls group. MSI status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled mononucleotide markers. The overall prevalence of MSI was 12.7 % (15 of 118 cases). MSI was detected mainly in mucinous adenocarcinoma (p\ 0.003), in high-grade tumors (p\ 0.008), in right-sided neoplasms (p = 0.05), and in patients with a better prognosis, though the difference was not statistically significant (11/59 patients -18.6 % vs 4/59 patients -6.7 %; OR 0.36, CI 95 % 0.11–1.15; p = 0.08). However, in multivariate analysis, MSI status becomes the strongest independent factor associated with relapse (OR 0.21, CI 95 % 0.06–0.82; p = 0.024), together with mucinous histological type (OR 6.08, CI 95 % 1.16–31.8; p = 0.032). MSI is a relevant prognostic factor in stage pT3N0M0 colon cancer suitable to discriminate those patients with a high risk of relapse. The online version of the original article can be found under doi:10.1007/s11739-015-1285-6. & Federica Domati federica.domati@unimore.it 1 Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy 2 Department of Pathology, University of Messina, Messina, Italy 3 Modena Cancer Registry, Modena, Italy 4 Department of Internal Medicine, Medicina I, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy 123 Intern Emerg Med (2016) 11:47 DOI 10.1007/s11739-015-1338-x