CD1a expression by Barrett's metaplasia of gastric type may help to predict its evolution towards cancer

Abstract

As emerging in the recent literature, CD1a has been regarded as a molecule whose expression may reflect tumour evolution. The aim of the present work was to investigate the expression of CD1a in a series of Barrett's metaplasia (BM), gastric type (GTBM), with and without follow-up, in order to analyse whether its expression may help to diagnose this disease and to address the outcome. Indeed, GTBM may be confused sometimes with islets of ectopic gastric mucosa and its evolution towards dysplasia (Dy) or carcinoma (Ca) could not be foreseen. We showed a significant higher expression of CD1a in GTBM than in both Dy and Ca; nevertheless, the number of positive GTBM was significantly lower in the group of cases that at follow-up underwent Dy or Ca. Our data address that CD1a may be a novel biomarker for BM and that its expression may help to predict the prognosis of this pathology. CD1a is a surface glycoprotein of 43 -49 kDa that has been shown to be expressed by dendritic cells (DCs), cortical thymocytes and Langerhans cells of the skin (Dezutter-Dambuyant et al, 1990;Krenacs et al, 1993;Gregory et al, 2000). Moreover, the research of CD1a is commonly used to differentiate various cutaneous T-cell lymphomas from B-cell lymphomasand pseudolymphomas (Arai et al, 1999;Schmuth et al, 2001).The antitumoral role of CD1a was recently proposed (Coventry and Morton, 2003a;Coventry and Heinzel, 2004;La Rocca et al, 2004). We also recently described that CD1a could be expressed in metaplastic epithelium of Barrett's oesophagus, both gastric and intestinal types, while normal gastric and colonic mucosa were negative to this marker (Cappello et al, 2003). In particular, we postulated that this marker may be useful in diagnosing Barrett's metaplasia (BM) and we hypothesised that its expression could predict a favourable outcome of this disease (Cappello, 2004).Indeed, BM may evolve towards dysplasia (Dy) or carcinoma (Ca) (Cameron and Carpenter, 1997; Malhi-Chowla et al, 2000;Moreto, 2003). Nevertheless, to date, we do not have any marker that could help to predict BM evolution.The aim of the present work was to detect CD1a expression in a large series of BM, Dy and Ca at the time of diagnosis and at follow-up. We would verify the diagnostic role of CD1a for BM and confirm our hypothesis concerning its prognostic role. MATERIALS AND METHODS Sample collectionWe selected retrospectively from our files, 222 cases as follows: 166 specimens were BM of gastric type (GTBM) that underwent follow up; moreover, we selected 37 specimens of Dy and 19 of Ca that did not undergo follow-up. Finally, as control group, we selected 10 specimens from normal gastric mucosa. Sample collection was performed according to ethical standards. In addition, we collected, from the 166 cases of GTBM, the specimens that underwent follow-up, commonly between 12 and 36 months from first diagnosis; in 134 cases, the diagnosis of BM was confirmed (FU-GTBM), while in 23 cases, GTBM evolved towards dysplasia (FU-Dy) and in nine cases towards carcinoma (FU-Ca). Imm...

CD1a down‐regulation in primary invasive ductal breast carcinoma may predict regional lymph node invasion and patient outcome

“…This is similar to our recent findings regarding metaplasiaadenocarcinoma progression in Barrett's oesophagus, 5,6 which led us to hypothesize a possible co-stimulatory effect of this molecule on the functional immune response. 7 The present data suggest that evaluation of CD1a expression at the LN level by means of molecular diagnostic analyses might help to address the presence of occult micrometastases.…”

“…The reaction was carried out using a two-step protocol, with a MyCycler thermal Cycler (BioRad, Milan, Italy). RT-PCR was carried out by mixing 2 g of total RNA, 0.5 lg of pd (T) [12][13][14][15][16][17][18] , 1 lg of pd (N) 6 with RNase-free water. The reaction comprised a reverse transcription step of 30 min (42°C), followed by inactivation of the enzyme at 95°C (5 min).…”

“…6 Indeed, CD1a may be expressed not only by DCs but also by transformed epithelial cells in BM. The interaction between DCs, CD1a-immunoreactive epithelial cells and T cells might potentiate the antitumour defence, at least in BM.…”

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

“…[18][19][20] CD1a has also been tested as a possible biomarker of Barrett's metaplasia, in the hope that its expression might help in predicting the prognosis of this pathology. 21 The markers p53 and c-erbB2 in particular have been controversially discussed. TP53 was found to have a low sensitivity, but p53 mutational status may ultimately be a component of such a molecular marker panel.…”

Dendritic Cell-Associated Immune Inflammation of Cardiac Mucosa: A Possible Factor in the Formation of Barrett’s Esophagus

“…[9][10][11] A variety of inflammatory and immune cells populate the Barrett's esophagus mucosa, including T and B lymphocytes, mast cells, and macrophages. [12][13][14] We recently reported that antigen-presenting dendritic cells are present in Barrett's esophagus with a significant increase in their spatial density in adenocarcinoma compared to benign Barrett's esophagus. 14 Dendritic cells are powerful initiators and regulators of immune reactions [15][16][17][18][19] and thus may have a role in the pathogenesis of Barrett's esophagus and adenocarcinoma.…”