TenascinC and type I and III collagen expression in total Achilles tendon rupture. An immunohistochemical study

Tendon tissue degeneration and changes in collagen composition play a role in spontaneous rupture of the human Achilles tendon. Tenascin-C has been shown to be present in the tissue pathology and changes in tissue loading. We made an immunohistological study of the expression of tenascin-C and type I and III collagens in ruptured human Achilles tendons. METHODS: Three tissue samples in ten individuals, one from the Achilles tendon rupture and two control samples from four and sixteen centimeters proximal in same tendon were collected at surgery. The specimen were fixed and labelled with specific antibodies to type I and III procollagens (PICP, PINP and PIIINP), mature type III collagen (IIINTP) and tenascin-C. The amount of reacting tissue was evaluated visually and graded on a semiquantitative scale. RESULTS: No difference in the expression of tenascin-C was found between the sites. Instead, mature type III collagen content (p=0.008) and type III collagen synthesis (p=0.016) were significantly increased at the rupture site relative to the control site 2. The amount of newly synthesized type I collagen (PINP, PICP) was relatively high at all sites, as expected. CONCLUSION: The expression of type III collagen is increased at the rupture site in the human Achilles tendon, but that of tenascin-C remains unchanged. This finding supports a tissue composition alteration background for Achilles tendon rupture, while the role of mechanical loading at the rupture site remains controversial

Risk of progression in Barrett’s esophagus based on diagnoses of general and gastrointestinal pathologists:a retrospective case-control study from Northern and Central Finland

Abstract Background: Esophageal adenocarcinoma (EAC) is the sixth leading cause of cancer-related death worldwide. It develops through Barrett’s metaplasia — dysplasia sequence. However, the effectiveness of endoscopic surveillance is limited, since diagnosis of low-grade dysplasia (LGD) is known to be challenging for pathologists. Our aim was to compare the risk of Barrett’s progression based on diagnoses of general and expert gastrointestinal (GI) pathologists in a population-based cohort. Methods: A total of 60 patients with non-dysplastic metaplasia (BE) or LGD progressing to high grade dysplasia (HGD) or EAC during follow-up could be identified in the population. For comparison, series representing non-progressive BE (n = 56) and LGD cases (n = 54), matched for age, gender, and length of follow-up were collected. All available original HE stained slides (n = 292) were blindly re-evaluated by two experienced GI pathologists and patient groups of progressive non-progressive BE and LGD were formed according to revised diagnoses. Results: Original diagnosis for each sample was changed in 25% of BE, 59% of LGD, and 33% of HGD diagnoses. Of the original LGD diagnoses, 53% were downgraded to BE or indefinite for dysplasia (ID). Of LGD diagnoses made by an expert GI pathologist, 61% were in the progressive LGD group, whereas only 42% of general pathologists’ LGD diagnoses were in the progressive LGD group. Conclusion: Based on this retrospective case-control study, LGD is strongly over-diagnosed among general pathologists. LGD diagnosed by expert GI pathologists predicts progressive disease. Recommendation for consensus diagnosis by expert GI pathologists is justified also in the Finnish population-based setting

Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett’s esophagus : a matched case-control study

Barrett’s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett’s metaplasia and low-grade dysplasia. This was a retrospective matched case–control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett’s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett’s metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett’s metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett’s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd’s ratio 6.7, 95% CI 1.8–24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case–control study, p53 expression associated with a high risk of malignant progression in Barrett’s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.peerReviewe