- Email: [email protected]
EXTRAINTESTINAL MANIFESTATIONS OF FAMILIAL ADENOMATOUS POLYPOSIS: THYROID MALIGNANT DISEASE
S118
Abstracts / Digestive and Liver Disease 41S (2009), S1–S167
erated. In fact, when we compared APCMin/+ mice (control group) with those fed on silymarin and silymarin + lignin a highly significant decrease of BrdU labeled intestinal epithelial cells was observed in the adenomatous mucosa; cell apoptosis was significantly increased both in the adenomatous tissue and in “normal” surrounding mucosa, and a significantly accelerated cell migration after BrdU labeling was observed. Silymarin and silymarin + lignin restored ERβ/ERalpha mRNA in APCMin/+ to levels comparable with WT syngeneic mice. When compared to APC Min/+ mice fed on the standard diet, ERβ mRNA resulted strikingly increased in all the dietary managed groups, whereas ERalpha mRNA resulted substantially unchanged. Conclusions: Our data demonstrate that the specific combination of silymarin and lignin is able to counteract intestinal tumorigenesis and supporting the role of a dietary-driven ERβ up-regulation as a potential chemopreventive approach against CRC development. # J. GI Oncology 7. Colon cancer
P.117 EXTRAINTESTINAL MANIFESTATIONS OF FAMILIAL ADENOMATOUS POLYPOSIS: THYROID MALIGNANT DISEASE V. Stigliano, L. Sanchez Mete, R. Baldelli, M.L. Appetecchia Regina Elena Cancer Institute, Roma Background and aim: Familial Adenomatous Polyposis (FAP) is an autosomal dominant inherited syndrome characterized by hundred to thousand colorectal adenomatous polyps with cancerization lifetime risk of 100%. Affected individuals are at increased risk to develop extraintestinal tumours such as thyroid and pancreatic ones, hepatoblastomas, medulloblastomas and benign tumours (adrenal adenomas, osteomas, desmoids tumours etc). Lifetime risk to develop thyroid carcinoma has been described about 2-3%, mainly in females, mean age 30 years. About 95% are papillary carcinoma, mostly multifocal. A minor variant recently described is the cribriform pattern. Utility of thyroid ultrasonographic surveillance is still controversial. Aim of this study was to evaluate the prevalence of malignant thyroid disease in individuals affected with FAP. Material and methods: 50 subjects from 34 FAP families were selected (27 F/23 M), mean age (±sd) at diagnosis was 29,1±10,9 years. All patients underwent blood examination for thyroid hormones and antibodies, ecocolordoppler ultrasonography and endocrinologic specialistic evaluation. Results: In 9/50 subjects an eumetabolic thyroid disease was found: plurinodular disease in 4; single nodule in 4; a malignant nodule in 1, histologically characterized after total tiroidectomy as papillary carcinoma. Conclusions: In the population examined the estimated prevalence of thyroid malignant disease was 2%. These preliminary results are in agreement with those of scientific literature, but need to be furtherly evaluate on a bigger population, in order to acquire enough data to assess utility of morpho-functional surveillance o thyroid in FAP series. # J. GI Oncology 7. Colon cancer
P.118 Pias3 AND ALR: NEW MARKERS FOR COLORECTAL CANCER EVALUATION IN HUMAN L. Polimeno ∗ ,1 , B. Pesetti 1 , F. Giorgio 1 , R.M. Notarnicola 1 , D. Piscitelli 2 , E. Annoscia 1 , A. Francavilla 1 1 Università di Bari - Sezione di Gastroenterologia ed Endoscopia Digestiva - Deto, Bari; 2 Università di Bari - Dipartimento di Anatomia Patologica, Bari
Background and aim: Human colorectal cancer (CRC), one of the
most frequent causes of death in the western world, is characterized by a sequence of biological events that determine its induction and progression. An important role in this multi step model of cell transformation has been attributed to activated Stat3 (P-Stat3), a factor able to regulate anti-apoptotic gene expression. Recently, we have demonstrated that Augmenter of Liver Regeneration (ALR) is a powerful inhibitor of apoptosis in regenerating rat liver after 70% hepatectomy. We have also showed that this effect is due to activation of Stat3 both in vivo and in vitro. Another regulator of P-Stat3 is Pias3, which is able to block its activity. Material and methods: The aim of the present study was to evaluate in human CRC tissue samples, by immunohistochemistry, the balance between Pias3, P-Stat3, ALR, cell proliferation (Ki-67), and apoptosis (Bcl2) expressions. Neoplastic tissue samples from twenty patients affected by CRC were evaluated. Results: The results are reported in the table, in which it is clearly demonstrated the presence of two subsets of patients. The first includes 8 patients with a strong positivity for P-Stat3, ALR, Bcl2 and negativity for Pias3. All the patients from this group show a strong positivity for Ki67, indicating that the inhibition of apoptosis allows active proliferation. On the contrary, the second subset includes 12 patients in which Pias3 is positive and the other parameters are negative, showing that inhibition of P-Stat3 is a key factor for inhibition of expression of Bcl2 and Ki67. n
P-Stat3
Pias3
ALR
Bcl2
Ki67
8 strongly positive negative positive strongly positive strongly positive 12 negative strongly positive negative weakly positive weakly positive n, no. of patients.
Conclusions: These results show the important role of ALR in regulating apoptosis by activation of P-Stat3. These data also demonstrate that the role of this factor is not only important in physiological conditions but plays an important role also in neoplastic diseases. In addition, these results indicate that the immunohistochemical determination of Pias3 and ALR may represent an efficient parameter to determine the proliferative activity of human colorectal cancer. # J. GI Oncology 7. Colon cancer
P.119 ADAM-9 PROMOTES CELL PROLIFERATION AND EXTRACELLULAR-MATRIX INVASION IN HUMAN PANCREATIC CANCER CELL LINES T. Mello ∗ ,1 , V. Foresta 1 , L. Cioni 1 , B. Ottanelli 1 , F. Buccoliero 1 , S. Polvani 2 , M. Tarocchi 1 , F. Lisi 1 , E. Ceni 1 , S. Milani 1 , C. Surrenti 1 , A. Galli 1 1
Università degli Studi di Firenze, Firenze; 2 Fiorgen Foundation, Firenze
Background and aim: A disintregrin and metalloproteases (ADAMs) are a fast growing family of proteolytic enzymes whose members have recently been shown to be disregulated in a variety of human cancers. The potential role for the ADAMs family in cancer relates to their extracellular-matrix proteolytic activity but also to their potential involvement in the cell-cell and cell-matrix interactions, as well as the shedding action of some members in the Notch, TNF-α and EGF signaling pathways. ADAM-9 exists as a transmenbrane and a soluble (ADAM9s) isoform and has been previously reported to be up-regulated in the epithelial component of human pancreatic cancers. Moreover, ADAM9 expression in PDAC seems to be a prognostic factor inversely related to patient survival. However, the role of ADAM9 in pancreatic cancer progression is still largely unknown. Therefore we aimed to further characterize the biological functions of ADAM9 in pancreatic cancer. Material and methods: Six pancreatic cancer cell lines (Panc-1, Su86,
Abstracts / Digestive and Liver Disease 41S (2009), S1–S167
erated. In fact, when we compared APCMin/+ mice (control group) with those fed on silymarin and silymarin + lignin a highly significant decrease of BrdU labeled intestinal epithelial cells was observed in the adenomatous mucosa; cell apoptosis was significantly increased both in the adenomatous tissue and in “normal” surrounding mucosa, and a significantly accelerated cell migration after BrdU labeling was observed. Silymarin and silymarin + lignin restored ERβ/ERalpha mRNA in APCMin/+ to levels comparable with WT syngeneic mice. When compared to APC Min/+ mice fed on the standard diet, ERβ mRNA resulted strikingly increased in all the dietary managed groups, whereas ERalpha mRNA resulted substantially unchanged. Conclusions: Our data demonstrate that the specific combination of silymarin and lignin is able to counteract intestinal tumorigenesis and supporting the role of a dietary-driven ERβ up-regulation as a potential chemopreventive approach against CRC development. # J. GI Oncology 7. Colon cancer
P.117 EXTRAINTESTINAL MANIFESTATIONS OF FAMILIAL ADENOMATOUS POLYPOSIS: THYROID MALIGNANT DISEASE V. Stigliano, L. Sanchez Mete, R. Baldelli, M.L. Appetecchia Regina Elena Cancer Institute, Roma Background and aim: Familial Adenomatous Polyposis (FAP) is an autosomal dominant inherited syndrome characterized by hundred to thousand colorectal adenomatous polyps with cancerization lifetime risk of 100%. Affected individuals are at increased risk to develop extraintestinal tumours such as thyroid and pancreatic ones, hepatoblastomas, medulloblastomas and benign tumours (adrenal adenomas, osteomas, desmoids tumours etc). Lifetime risk to develop thyroid carcinoma has been described about 2-3%, mainly in females, mean age 30 years. About 95% are papillary carcinoma, mostly multifocal. A minor variant recently described is the cribriform pattern. Utility of thyroid ultrasonographic surveillance is still controversial. Aim of this study was to evaluate the prevalence of malignant thyroid disease in individuals affected with FAP. Material and methods: 50 subjects from 34 FAP families were selected (27 F/23 M), mean age (±sd) at diagnosis was 29,1±10,9 years. All patients underwent blood examination for thyroid hormones and antibodies, ecocolordoppler ultrasonography and endocrinologic specialistic evaluation. Results: In 9/50 subjects an eumetabolic thyroid disease was found: plurinodular disease in 4; single nodule in 4; a malignant nodule in 1, histologically characterized after total tiroidectomy as papillary carcinoma. Conclusions: In the population examined the estimated prevalence of thyroid malignant disease was 2%. These preliminary results are in agreement with those of scientific literature, but need to be furtherly evaluate on a bigger population, in order to acquire enough data to assess utility of morpho-functional surveillance o thyroid in FAP series. # J. GI Oncology 7. Colon cancer
P.118 Pias3 AND ALR: NEW MARKERS FOR COLORECTAL CANCER EVALUATION IN HUMAN L. Polimeno ∗ ,1 , B. Pesetti 1 , F. Giorgio 1 , R.M. Notarnicola 1 , D. Piscitelli 2 , E. Annoscia 1 , A. Francavilla 1 1 Università di Bari - Sezione di Gastroenterologia ed Endoscopia Digestiva - Deto, Bari; 2 Università di Bari - Dipartimento di Anatomia Patologica, Bari
Background and aim: Human colorectal cancer (CRC), one of the
most frequent causes of death in the western world, is characterized by a sequence of biological events that determine its induction and progression. An important role in this multi step model of cell transformation has been attributed to activated Stat3 (P-Stat3), a factor able to regulate anti-apoptotic gene expression. Recently, we have demonstrated that Augmenter of Liver Regeneration (ALR) is a powerful inhibitor of apoptosis in regenerating rat liver after 70% hepatectomy. We have also showed that this effect is due to activation of Stat3 both in vivo and in vitro. Another regulator of P-Stat3 is Pias3, which is able to block its activity. Material and methods: The aim of the present study was to evaluate in human CRC tissue samples, by immunohistochemistry, the balance between Pias3, P-Stat3, ALR, cell proliferation (Ki-67), and apoptosis (Bcl2) expressions. Neoplastic tissue samples from twenty patients affected by CRC were evaluated. Results: The results are reported in the table, in which it is clearly demonstrated the presence of two subsets of patients. The first includes 8 patients with a strong positivity for P-Stat3, ALR, Bcl2 and negativity for Pias3. All the patients from this group show a strong positivity for Ki67, indicating that the inhibition of apoptosis allows active proliferation. On the contrary, the second subset includes 12 patients in which Pias3 is positive and the other parameters are negative, showing that inhibition of P-Stat3 is a key factor for inhibition of expression of Bcl2 and Ki67. n
P-Stat3
Pias3
ALR
Bcl2
Ki67
8 strongly positive negative positive strongly positive strongly positive 12 negative strongly positive negative weakly positive weakly positive n, no. of patients.
Conclusions: These results show the important role of ALR in regulating apoptosis by activation of P-Stat3. These data also demonstrate that the role of this factor is not only important in physiological conditions but plays an important role also in neoplastic diseases. In addition, these results indicate that the immunohistochemical determination of Pias3 and ALR may represent an efficient parameter to determine the proliferative activity of human colorectal cancer. # J. GI Oncology 7. Colon cancer
P.119 ADAM-9 PROMOTES CELL PROLIFERATION AND EXTRACELLULAR-MATRIX INVASION IN HUMAN PANCREATIC CANCER CELL LINES T. Mello ∗ ,1 , V. Foresta 1 , L. Cioni 1 , B. Ottanelli 1 , F. Buccoliero 1 , S. Polvani 2 , M. Tarocchi 1 , F. Lisi 1 , E. Ceni 1 , S. Milani 1 , C. Surrenti 1 , A. Galli 1 1
Università degli Studi di Firenze, Firenze; 2 Fiorgen Foundation, Firenze
Background and aim: A disintregrin and metalloproteases (ADAMs) are a fast growing family of proteolytic enzymes whose members have recently been shown to be disregulated in a variety of human cancers. The potential role for the ADAMs family in cancer relates to their extracellular-matrix proteolytic activity but also to their potential involvement in the cell-cell and cell-matrix interactions, as well as the shedding action of some members in the Notch, TNF-α and EGF signaling pathways. ADAM-9 exists as a transmenbrane and a soluble (ADAM9s) isoform and has been previously reported to be up-regulated in the epithelial component of human pancreatic cancers. Moreover, ADAM9 expression in PDAC seems to be a prognostic factor inversely related to patient survival. However, the role of ADAM9 in pancreatic cancer progression is still largely unknown. Therefore we aimed to further characterize the biological functions of ADAM9 in pancreatic cancer. Material and methods: Six pancreatic cancer cell lines (Panc-1, Su86,