Jónas Magnússon

Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland

Recent studies have described a spasmolytic polypeptide-expressing metaplastic cell lineage (SPEM) in the gastric fundic mucosa associated with both chronic H. pylori infection and gastric adenocarcinoma. We investigated the association of SPEM both with early gastric adenocarcinoma and in biopsies taken from patients prior to diagnosis of cancer. Two cohorts were examined. First, gastric resections from 29 patients with early gastric cancer were examined. Second, biopsies taken from 18 patients prior to the diagnosis of gastric cancer were compared with their respective resection specimens as well as with control biopsies from a cohort of 19 patients diagnosed with gastritis without subsequent development of cancer. The presence of SPEM and intestinal metaplasia (IM) adjacent to and distant from the cancer was compared and spasmolytic polypeptide (SP) immunostaining within dysplastic/cancerous cells was identified. SPEM was present adjacent to cancer in all early cancer cases where the tumor was located in the body or at the body/antrum junction, and was present in the body mucosa distant from the cancer in 76% of cases. Intestinal metaplasia was found adjacent to the tumor in 76% of cases and in body sections in 52% of resections. SP immunostaining was noted within cancer cells in 62% of tumors, and within dysplastic cells in 76% of resections where dysplasia was present. SPEM was present in 82% of the biopsies obtained prior to the diagnosis of cancer, compared with only 37% in the gastritis cohort. IM was present in only 57% of biopsies. In conclusion, SPEM is strongly associated with early gastric cancers and is observed in gastric biopsies prior to the development of cancer. In addition, early gastric cancers demonstrated a high incidence of SP expression. These results suggest that SPEM merits consideration as an important pre-neoplastic gastric lesion.

Alterations of E-cadherin and β-catenin in gastric cancer

BackgroundThe E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression.MethodsWe studied the alterations of E-cadherin and β-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC).ResultsA high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and β-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for β-catenin IHC. An association was found between reduced expression of E-cadherin and β-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype.ConclusionOur results support the hypothesis that alterations of E-cadherin and β-catenin play a role in the initiation and progression of gastric cancer.

Renal oncocytoma: a clinicopathological analysis of 45 consecutive cases.

To evaluate the clinical behaviour and pathology of renal oncocytoma in a well‐defined population over a 30‐year period.

A population-based analysis of survival and incidental diagnosing of renal cell carcinoma patients in Iceland, 1971-1990

The significance of incidental diagnosing in relation to survival of renal cell carcinoma (RCC) patients is not known. A retrospective, population-based study was carried out in order to evaluate the survival of RCC patients, with emphasis on incidental diagnosing. Included in the study were all patients diagnosed with RCC in Iceland between 1971 and 1990. The tumours were classified and the extent of the disease staged by Robsons method. Crude probability of survival was evaluated for every stage, and multivariate analysis applied in order to determine prognostic factors. Out of 408 patients, 15% were diagnosed incidentally between 1971 and 1980 and 20% between 1981 and 1990 (p > 0.1), most often by intravenous urography. Only 5 tumours were detected incidentally by ultrasound techniques and 4 by CT scans. Crude five-year survival was 76% for stage I disease and 11% for stage IV disease. After correction for staging by multivariate analysis, incidental diagnosis and the year of diagnosis were not independent significant prognostic factors for mortality. As in many other studies, our data indicate that incidentally diagnosed RCCs are at a lower stage at the time of diagnosis. On the other hand, the results of our population-based study show that ultrasound and CT scanning have not significantly increased the number of incidentally diagnosed tumours. It is therefore not very surprising that surviving of RCC patients in Iceland has remained the same for the last two decades.

Renal cell carcinoma in young compared to older patients: Comparison of clinicopathological risk factors and survival

Objective. Renal cell carcinoma (RCC) is primarily a disease of the elderly, most patients being diagnosed in their mid-60s. However, a significant number of patients are diagnosed at a younger age. The true effect of age at diagnosis on survival has been debated, tumor stage and grade being the strongest prognostic factors of survival. The aim of this nationwide study was to study the significance of young age at diagnosis as a prognostic factor in RCC. Material and methods. This retrospective study included all living patients with histologically verified RCC in Iceland diagnosed between 1971 and 2000 (n=629). Different clinicopathological factors of patients diagnosed aged <50 years (n=99) were compared to those of patients diagnosed aged ≥50 years (n=530). Disease-specific survival was compared and multivariate analysis was used to evaluate prognostic variables. Results. Clinical presentation, TNM stage, grade, tumor size and histological subtypes were comparable between the two groups. Prognostic factors were the same in both groups, most of them having a stronger prognostic value in younger patients. Both 5- and 10-year disease-specific survival was significantly higher in the younger group (66.4% vs 54.5% at 5 years). Conclusions. The clinicopathological profiles are comparable in RCC patients aged < and ≥ 50 years. The reason for the more favorable survival of younger patients is not known. Further studies are needed, including studies on possible differences in age-specific host–tumor response.