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Di Tommaso, Luca,Destro, Annarita,Seok, Jae Yeon,Balladore, Emanuela,Terracciano, Luigi,Sangiovanni, Angelo,Iavarone, Massimo,Colombo, Massimo,Jang, Ja June,Yu, Eunsil,Jin, So Young,Morenghi, Emanuela Elsevier 2009 Journal of hepatology Vol.50 No.4
<P><B>Background/Aims</B></P><P>Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC.</P><P><B>Methods</B></P><P>We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (<I>n</I>=13), low-grade dysplastic nodules (<I>n</I>=21), high-grade dysplastic nodules (<I>n</I>=50), very well-differentiated (VWD) (<I>n</I>=17), well-differentiated (WD-G1) (<I>n</I>=40) and G2-3 (<I>n</I>=35) HCC.</P><P><B>Results</B></P><P>Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity.</P><P><B>Conclusions</B></P><P>This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.</P>
Affinity for self antigen selects T<sub>reg</sub> cells with distinct functional properties
Wyss, Lena,Stadinski, Brian D,King, Carolyn G,Schallenberg, Sonja,McCarthy, Nicholas I,Lee, Jun Young,Kretschmer, Karsten,Terracciano, Luigi M,Anderson, Graham,Surh, Charles D,Huseby, Eric S,Palmer, E Nature Publishing Group, a division of Macmillan P 2016 NATURE IMMUNOLOGY Vol.17 No.9
<P>The manner in which regulatory T cells (T-reg cells) control lymphocyte homeostasis is not fully understood. We identified two T-reg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) T-reg cells were highly self-reactive and controlled lympho-proliferation in peripheral lymph nodes. GITR(lo)PD-1(lo)CD25(lo) (Triple(lo)) T-reg cells were less self-reactive and limited the development of colitis by promoting the conversion of CD4(+) T-conv cells into induced T-reg cells (iT(reg) cells). Although Foxp3-deficient (Scurfy) mice lacked T-reg cells, they contained Triple(hi)-like and Triple(lo)-like CD4(+) T cells with distinct pathological properties. Scurfy Triple(hi)CD4(+) T cells infiltrated the skin, whereas Scurfy. Triple(lo)CD4(+) T cells induced colitis and wasting disease. These findings indicate that the affinity of the T cell antigen receptor for self antigen drives the differentiation of T-reg cells into distinct subsets with non-overlapping regulatory activities.</P>
Di Tommaso, Luca,Franchi, Giada,Park, Young Nyun,Fiamengo, Barbara,Destro, Annarita,Morenghi, Emanuela,Montorsi, Marco,Torzilli, Guido,Tommasini, Maurizio,Terracciano, Luigi,Tornillo, Luigi,Vecchione, Wiley Subscription Services, Inc., A Wiley Company 2007 Hepatology Vol.45 No.3
<P>Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725–734.)</P>