Search

Background: Autoimmune gastritis (AIG) is a gastric pathologic condition affecting the mucosa of the fundus and the body and eventually leading to hypo-achlorhydria., Aims: We report our clinical and pathological experience with AIG., Methods: Data from patients with a diagnosis of AIG seen in the period January 2002-December 2012 were retrieved. Only patients with complete sets of biopsies were analyzed., Results: Data from 138 patients were available for analysis. Pernicious anemia was present in 25% of patients, iron deficiency anemia was found in 29.7% of patients, hypothyroidism in 23% of patients, type 1 diabetes in 7.9% of patients, and vitiligo in 2.8% of patients. Parietal cell antibodies were positive in 65% of patients, and no patient had serology positive for celiac disease. All gastric biopsies showed glandular atrophy associated with enterochromaffin-like (ECL)-cells hyperplasia, features limited to the mucosa of the fundus and body, and focal glandular intestinal metaplasia. Helicobacter pylori was negative in all cases., Conclusions: AIG was strongly associated with anemia; atrophy, intestinal metaplasia and ECL hyperplasia in the gastric fundus and body are hallmarks of this condition.

Little is known about the complex signaling architecture of KRAS and the interconnected RAS-driven protein-protein interactions, especially as it occurs in human clinical specimens. This study explored the activated and interconnected signaling network of KRAS mutant lung adenocarcinomas (AD) to identify novel therapeutic targets.Thirty-four KRAS mutant (MT) and twenty-four KRAS wild-type (WT) frozen biospecimens were obtained from surgically treated lung ADs. Samples were subjected to Laser Capture Microdissection and Reverse Phase Protein Microarray analysis to explore the expression/activation levels of 150 signaling proteins along with co-activation concordance mapping. An independent set of 90 non-small cell lung cancers (NSCLC) was used to validate selected findings by immunohistochemistry (IHC).Compared to KRAS WT tumors, the signaling architecture of KRAS MT ADs revealed significant interactions between KRAS downstream substrates, the AKT/mTOR pathway, and a number of Receptor Tyrosine Kinases (RTK). Approximately one-third of the KRAS MT tumors had ERK activation greater than the WT counterpart (p<0.01). Notably 18% of the KRAS MT tumors had elevated activation of the Estrogen Receptor alpha (ER-α) (p=0.02).This finding was verified in an independent population by IHC (p=0.03).KRAS MT lung ADs appear to have a more intricate RAS linked signaling network than WT tumors with linkage to many RTKs and to the AKT-mTOR pathway. Combination therapy targeting different nodes of this network may be necessary to treat this group of patients. In addition, for patients with KRAS MT tumors and activation of the ER-α, anti-estrogen therapy may have important clinical implications.

Aims and Background: The aim of this retrospective multicenter study was to evaluate the impact of progesterone receptor (PgR) loss on locoregional recurrence in patients with estrogen receptor (ER)-positive primary breast cancer and ER-positive locoregional recurrence., Patients and Methods: Eight Italian oncology centers collected data from consecutive patients with ER-positive breast cancer and a subsequent ER-positive locoregional recurrence., Results: Data were available for 265 patients diagnosed with breast cancer between 1990 and 2009. Median metastasis-free survival was 111 months in patients with PgR-positive primary tumors and locoregional recurrence (PgRpos), 38 months in patients with PgR-negative primary tumors and locoregional recurrence (PgRneg), and 63 months in patients with PgR-positive primary tumors and PgR-negative locoregional recurrence (PgRloss). In multivariate analysis, PgR status was independently associated with metastasis-free survival, with a hazard ratio of 2.84 (95% CI 1.34-6.00) for PgRneg compared with PgRpos, and 2.93 (95% CI: 1.51-5.70) for PgRloss compared with PgRpos., Conclusions: PgR absence was found to be a negative prognostic factor in breast cancer patients with ER-positive locoregional recurrence. Thus, PgR status could be a biological marker in ER-positive recurrent breast cancer.

Gastrointestinal stromal tumor (GIST) natural history per se has not been extensively investigated yet, with most data being drawn from large studies with a relevant referral bias. Hence, the estimation of prognosis still remains a critical issue. We retrospectively evaluated 929 GISTs resected between 1980 and 2000 in 35 Italian institutions. A total of 526 patients were found to be suitable for refining risk assessment through the development of a survival nomogram. Median follow-up was 126 months. On testing for potential prognostic parameters, age, tumor site, size, and mitotic index proved to be predictors of OS on both univariable and multivariable Cox model analyses, whereas necrosis and cytonuclear atypia were significant on univariable analysis only. The discriminative ability of the model, including the parameters selected after a backward procedure (C=0.72), improved compared with the National Institutes of Health 2002 (C=0.64) and the National Comprehensive Cancer Network 2007 (C=0.63). On the basis of these data we developed a prognostic nomogram for survival that considers site, size, and mitotic index as continuous variables, providing estimates stratified for patients aged ≤65 and >65 years. This nomogram is a tool based on survival. It overcomes problems that result from artificial categorization of continuous variables. We believe that in the future this should also be attempted by nomograms based on the risk of relapse.

Aims and Background: The aim of this study was to evaluate the relationship between a panel of biological markers (p53, Bcl-2, HER-2, Ki67, DNA ploidy and S-phase fraction) and clinical-pathological parameters and its impact on outcome in non-small cell lung cancer (NSCLC)., Methods and Study Design: Tumor tissue specimens obtained after surgical resection were collected from consecutive patients with NSCLC. We used an immunocytochemical technique for p53, Bcl-2, HER-2 and Ki67 analysis in fine-needle aspirates obtained from surgical samples that were also evaluated by flow cytometric DNA analysis using a FACScan flow cytometer., Results: From April 2000 to December 2005, 136 patients with radically resected NSCLC were recruited. Median age was 66 years (range, 31-84 years), male/female ratio 117/19, ECOG performance status 0/1 127/4, stage I/II/III 76/25/35, squamous/adenocarcinoma/large-cell/mixed histology 62/49/17/8, smokers yes/no 121/11. Positivity of p53, Bcl-2, HER-2 and Ki67 was detected in 51.4%, 27.9%, 25.0% and 55.8% of the samples, respectively; 82.9% of the cases revealed aneuploid DNA histograms and 56.7% presented an S-phase fraction of more than 12%. Statistically significant associations between high Ki67 and poorly differentiated tumors (P = 0.016) and a smoking history (P = 0.053); p53 positivity and high Ki67 (P = 0.002); HER-2 positivity and adenocarcinoma subtype (P = 0.015) and presence of lymph node involvement (P = 0.006); and Bcl-2 positivity and squamous cell carcinoma subtype (P = 0.058) were observed. At univariate analysis, high Ki67 proved to be the only marker associated with disease-free survival (P = 0.047). After adjusting for stage, none of the examined immunocytochemical markers emerged as an independent factor for disease-free and overall survival; only pathological stage was identified as an independent prognostic factor for disease-free survival (P = 0.0001) and overall survival (P = 0.0001). In the group of 76 patients classified as TNM stage I, high Ki67 was the only marker associated with recurrence of disease (P = 0.05)., Conclusions: Our data do not support a relevant prognostic role of immunocytochemical markers in NSCLC, even if the Ki67 index might have particular relevance to identify patients with more aggressive tumors who are at high risk for disease relapse.

The search for single independent prognostic factors in breast cancer has often produced conflicting results. Therefore, prognostic indexes have been compiled by combining several parameters. In this study we compare the Nottingham Prognostic Index (NPI), which is based on traditional prognostic factors (diameter of the neoplasm, lymph node status and histological grade) with the Adelaide Prognostic Index (API), which is based on the tumour diameter and two biological parameters: oestrogen receptors and cell kinetics. We considered 82 cases of breast cancer observed over the period 1987-1990 with a minimum follow-up of 60 months. The NPI gives a better definition of the prognostic profile for each patient. Our results indicate three prognostic groups (good, moderate, unfavourable), which differ with respect to disease-free survival (DFS; P=0.0024) and overall survival (OS; P=0.0033). In contrast, the API scores showed no significant correlation with OS or DFS. The use of prognostic indexes, especially when compiled using traditional parameters, is a useful aid to the clinician, since they can provide a reliable indication of how individual tumours will evolve.

Literature data suggest that breast cancers occurring in young patients may be different from those arising in older women. In this study the clinicopathologic characteristics of 50 patients under 40 years of age were compared with those of patients aged over 60. Patients under 40 years old more frequently had a family history of breast cancer than did older patients (24% vs 17%) and had more often used oral contraceptives (29% vs 13%); on average they had experienced menarche 1 year earlier. For early onset breast carcinomas there was a higher frequency of grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs 58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2 overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate that breast cancers arising in young women have a significantly different biopathological profile from those in older patients, with a predominance of unfavourable prognostic parameters.

In order to document any modifications in age and sex distributions, tumor locations and histological types, a retrospective study was performed comparing 377 consecutive cases of gastric cancers observed from 1942 to 1956 with 359 cases diagnosed from 1986 to 1987. The mean age at diagnosis rose from 57 to 66 years with no significant male/female ratio variations (1.6 vs 1.7). Tumors located in the proximal stomach increased from 13 to 23% (p less than 0.001) whereas those arising in the distal stomach decreased from 66 to 50% (p less than 0.001). Intestinal type gastric carcinoma decreased from 65.6 to 52.6% (p less than 0.001). The diffuse type rose from 24 to 43% (p less than 0.001) and the mucoid type fell from 10.3 to 4.4% (p less than 0.001). In spite of the overall decline in intestinal type carcinomas, this form remained more common in the upper third area and increased from 55 to 70% (p less than 0.001). Significant modifications in the distribution of diffuse, mucoid and signet ring cell type carcinomas were also noted. The possible significance and implications of these observations are discussed.