Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target f... more Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.Results. HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.Conclusions. HER2 overexpression in premalignant gastric lesions suggests its potential involvem...
1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepato... more 1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepatoid carcinomas of the foregut. Caruso RA, Tuccari G. Comment on Pathology. 1995 Jul;27(3):277-9. PMID: 8912366 [PubMed - indexed for MEDLINE]. Publication Types: ...
Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in ass... more Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in association with low microvessel density (MVD). It competes with vascular endothelial growth factor (VEGF) for receptor neuropilin-1 (NRP-1). The ratio between VEGF and SEMA3A has been recently demonstrated to regulate neo-angiogenesis, proliferation and progression of tumors. To clarify the involvement of these proteins in the above-mentioned phenomena, we analyzed the immunohistochemical expression of SEMA3A, VEGF and NRP-1 and their correlation with MVD in a series of 48 cases of meningioma with different histotype and histological grade. SEMA3A and VEGF expression was encountered in about half the cases, although at different levels. NRP-1 staining was evidenced in the vessels within all but two tumors and in the neoplastic cells of 18/48 meningiomas. A negative significant correlation emerged between SEMA3A amount and MVD; on the other hand, high VEGF levels appeared to be significantly associated with high MVD. A high VEGF/SEMA3A was significantly associated with high histological grade, proliferation index and MVD as well as with a higher recurrence rate of the meningiomas. Present data suggest that the balance between the expression of the pro-angiogenic factor VEGF and the anti-angiogenic SEMA3A may be involved in the regulation of neo-angiogenesis and proliferation in meningiomas, representing also a predictor of recurrences in these tumors. Further validation of our results may open the way for the use of drugs targeting not only VEGF, but also NRP-1 and SEMA3A to prevent recurrences of meningiomas.
The simple mucin-type carbohydrate antigens Tn, sialosyl-Tn, T and the 'cryptic&a... more The simple mucin-type carbohydrate antigens Tn, sialosyl-Tn, T and the 'cryptic' sialylated variant of the last represent the mucin core oligosaccharide structures that are produced in the initial steps of the mucin biosynthetic pathway. Utilizing monoclonal antibodies anti-Tn antigen (HB-Tn1), anti-sialosyl-Tn antigen (HB-STn1), anti-T antigen (HB-T1) and the biotinylated Amaranthus caudatus agglutinin (ACA), we have investigated the expression of the simple mucin-type carbohydrate antigens in hereditary nonpolyposis colorectal cancer (HNPCC; 15 cases) compared with sporadic colorectal cancer (CRC; 60 cases) and normal colonic mucosa (30 cases). A variable positivity of Tn, sialosyl-Tn, T and the cryptic sialylated form of this latter antigen was encountered in both HNPCC and sporadic CRC cases; in addition, in normal colonic mucosa a constant reactivity was encountered only for Tn and the cryptic sialylated form of T, while negative results were always obtained for sialosyl-Tn and T antigens. Statistical analysis, performed using a Chi-square test, showed significantly lower (P = 0.037) expression of sialosyl-Tn and higher (P = 0.022) expression of T in HNPCC than in sporadic CRC, suggesting a greater presence of beta 1,3 galactosyltransferase activity in HNPCC than in sporadic CRC. We were unable to identify a peculiar phenotype for HNPCC with simultaneous evaluation of reactivity for HB-Tn1, HB-STn1, HB-T1 and ACA; the biological significance of the preferential expression of T antigen in HNPCC remains to be investigated.
Journal of Pediatric Gastroenterology and Nutrition, 1988
ABSTRACT Data on the frequency of regression of Barrett's esophagus after medical... more ABSTRACT Data on the frequency of regression of Barrett's esophagus after medical therapy or antireflux surgery in adult patients are conflicting; these data, with regard to Pediatric age, where Barrett's esophagus is considered rare, are scarce and disappointing after antireflux surgery. We report a 4-month-old infant affected by severe reflux esophagitis who developed a junctional-type Barrett's epithelium. Histochemical procedures to detect mucin pattern were also carried out. The regression of Barrett's esophagus was observed 4 months after antire-flux surgery whereas medical therapy had been unsuccessful. We suggest that esophageal biopsy should also be performed in the presence of severe esophagitis. Longer follow-up observations of other patients may clarify the role of antireflux surgery when Barrett's esophagus complicates gastroesophageal reflux (GER).
1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepato... more 1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepatoid carcinomas of the foregut. Caruso RA, Tuccari G. Comment on Pathology. 1995 Jul;27(3):277-9. PMID: 8912366 [PubMed - indexed for MEDLINE]. Publication Types: ...
Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This h... more Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This histological classification mirrors histogenetic hypotheses according to which the intestinal-type cancer derives from intestinal metaplasia and dysplasia, while the diffuse-type originates directly from gastric mucosa, with or without a preceding non-metaplastic dysplasia. Studies concerning mucins expression in gastric neoplastic and preneoplastic lesions have provided contradictory data concerning such histogenetic relationships. The aim of the present study was to verify whether a correlation between mucins phenotype and Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided, according to Laurèn's classification, into 27 intestinal-type, 10 diffuse-type and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical expression. Intestinal-type carcinomas displayed a MUC1-positive staining in 23/27 cases and a MUC2-positive immunoreaction in 10/2...
Hepatobiliary & Pancreatic Diseases International, 2015
ABSTRACT BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrate... more ABSTRACT BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic lesions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocytochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions. METHODS: A series of 46 pancreaticobiliary carcinomas with available cell block preparations was submitted to immunocytochemistry against cytokeratins, carcinoembryonic antigen, E-cadherin, CD10 and p53. The sensitivity, specificity, positive and negative predictive values of the cytological smear in the discrimination of malignant lesions were calculated and compared with those of cell block preparation with the immunocytochemical stains against p53 and CD10. RESULTS: According to our findings, the use of cell block preparations together with immunostains against p53 and CD10 allowed to discriminate malignant versus benign specimens with higher sensitivity than the only cytological examination. In detail, CD10 immunostaining was of significant help for the discrimination between cytological contaminants, such as benign gastrointestinal cells, and the neoplastic elements of pancreaticobiliary well differentiated adenocarcinomas. Also, intense nuclear immunoreactivity for p53 was encountered in about 2/3 of the cases and identified pancreatic malignancy with high sensitivity. CONCLUSIONS: We suggest that immunocytochemistry against both CD10 and p53 could be applied case by case, mainly to differentiate gastrointestinal and pancreatic benign cellular contaminants showing hyperplasia or reactive changes from differentiated pancreaticobiliary adenocarcinomas.
Since an aberrant glycosylation associated with abnormal expression of cell surface carbohydrates... more Since an aberrant glycosylation associated with abnormal expression of cell surface carbohydrates has been described in many human tumours, we have investigated the expression of simple mucintype carbohydrate antigens (Tn, sialosyl-Tn and T) in 30 formalin-fixed paraffin-embedded surgical specimens of primary meningiomas, subdivided according to the WHO classification as follows: 18 meningotheliomatous, 7 transitional, 2 angiomatous and 3 anaplastic; in addition, 5 meningeal samples taken at autopsy were tested as control. Specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1, Dako) were utilized with ABC method; the percentage of immunostained cells was graded as follows: O (no staining); 1 (> 0 to 5%); 2 (> 5 to 50%); 3 (> 50%). Tn antigen was not expressed in any case. Sialosyl-Tn antigen was demonstrated only in cases of anaplastic meningiomas (score 1-3). The immunoreactivity for T antigen was found in 2 cases of meningotheliomatous (score 1) and in all the anaplas...
European review for medical and pharmacological sciences, 2012
The odontoameloblastoma (OA), also known as ameloblastic odontoma, is a rare neoplasm of jaws whi... more The odontoameloblastoma (OA), also known as ameloblastic odontoma, is a rare neoplasm of jaws which includes odontogenic ectomesenchyme in addition to odontogenic epithelium that resembles an ameloblastoma both in structure and in behaviour. The exact incidence is difficult to determine. Since 1944, only 24 cases have been reported in English literature which fulfill both histological and clinical features of this lesion. The Authors report a case report of an odontoameloblastoma in a 15-year-old caucasian man treated with a surgical excision. The five years follow-up shows no evidence of recurrence confirming the validity of a conservative surgery with enucleation of OA, followed by periodical clinical and radiographical controls.
The diagnosis of celiac disease (CD) is still mainly based on pathological description. However, ... more The diagnosis of celiac disease (CD) is still mainly based on pathological description. However, these descriptions are often unable to identify latent CD. The aim of this study was to evaluate whether the Marsh-Oberhuber classification and a recently proposed classification may help to identify patients with latent CD. Biopsy samples from twelve patients with latent CD (age range 3-32 years) defined as having normal duodenal mucosa when ingesting a free diet, and subsequently developing severe villous atrophy, were retrospectively reviewed in blind according to the Marsh-Oberhuber classification and the new grading system. In 67% of patients the Marsh-Oberhuber and the new classification could have yielded a diagnosis of CD soon after the first biopsy (3a-3c score when reviewed according to this classification, and B2 score when reviewed according to the new grading system), thereby avoiding further (up to two more in four cases) unnecessary endoscopic procedures. Both the Marsh-Ob...
Using a sequential method for the simultaneous demonstration of lysozyme and mucins, the possible... more Using a sequential method for the simultaneous demonstration of lysozyme and mucins, the possible existence of a transitional cell intermediate in form between Paneth and goblet cells has been investigated in childhood coeliac disease. Mixed staining for both mucins and lysozyme has not been encountered within intestinal cells of affected mucosae and controls.
Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target f... more Objectives. HER2 expression in gastric cancer (GC) has received attention as a potential target for therapy with Trastuzumab. We reviewed the current knowledge on HER2 status in premalignant gastric lesions and in early (EGC) and advanced (AGC) GC to discuss the possible pathogenetic and prognostic roles of HER2 overexpression in GC.Results. HER2 overexpression was documented in gastric low-grade (LG) and high-grade intraepithelial neoplasia (HG-IEN), with higher frequency in gastric type dysplasia. HER2 overexpression was significantly associated with disease recurrence and poor prognosis in EGC representing an independent risk factor for lymph node metastases. HER2 overexpression was more frequent in AGC characterized by high grade, advanced stage, and high Ki-67 labeling index. The discordance in HER2 status was evidenced between primitive GC and synchronous or metachronous metastases.Conclusions. HER2 overexpression in premalignant gastric lesions suggests its potential involvem...
1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepato... more 1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepatoid carcinomas of the foregut. Caruso RA, Tuccari G. Comment on Pathology. 1995 Jul;27(3):277-9. PMID: 8912366 [PubMed - indexed for MEDLINE]. Publication Types: ...
Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in ass... more Semaphorin3A (SEMA3A) is an anti-angiogenic factor which is expressed in human meningiomas in association with low microvessel density (MVD). It competes with vascular endothelial growth factor (VEGF) for receptor neuropilin-1 (NRP-1). The ratio between VEGF and SEMA3A has been recently demonstrated to regulate neo-angiogenesis, proliferation and progression of tumors. To clarify the involvement of these proteins in the above-mentioned phenomena, we analyzed the immunohistochemical expression of SEMA3A, VEGF and NRP-1 and their correlation with MVD in a series of 48 cases of meningioma with different histotype and histological grade. SEMA3A and VEGF expression was encountered in about half the cases, although at different levels. NRP-1 staining was evidenced in the vessels within all but two tumors and in the neoplastic cells of 18/48 meningiomas. A negative significant correlation emerged between SEMA3A amount and MVD; on the other hand, high VEGF levels appeared to be significantly associated with high MVD. A high VEGF/SEMA3A was significantly associated with high histological grade, proliferation index and MVD as well as with a higher recurrence rate of the meningiomas. Present data suggest that the balance between the expression of the pro-angiogenic factor VEGF and the anti-angiogenic SEMA3A may be involved in the regulation of neo-angiogenesis and proliferation in meningiomas, representing also a predictor of recurrences in these tumors. Further validation of our results may open the way for the use of drugs targeting not only VEGF, but also NRP-1 and SEMA3A to prevent recurrences of meningiomas.
The simple mucin-type carbohydrate antigens Tn, sialosyl-Tn, T and the 'cryptic&a... more The simple mucin-type carbohydrate antigens Tn, sialosyl-Tn, T and the 'cryptic' sialylated variant of the last represent the mucin core oligosaccharide structures that are produced in the initial steps of the mucin biosynthetic pathway. Utilizing monoclonal antibodies anti-Tn antigen (HB-Tn1), anti-sialosyl-Tn antigen (HB-STn1), anti-T antigen (HB-T1) and the biotinylated Amaranthus caudatus agglutinin (ACA), we have investigated the expression of the simple mucin-type carbohydrate antigens in hereditary nonpolyposis colorectal cancer (HNPCC; 15 cases) compared with sporadic colorectal cancer (CRC; 60 cases) and normal colonic mucosa (30 cases). A variable positivity of Tn, sialosyl-Tn, T and the cryptic sialylated form of this latter antigen was encountered in both HNPCC and sporadic CRC cases; in addition, in normal colonic mucosa a constant reactivity was encountered only for Tn and the cryptic sialylated form of T, while negative results were always obtained for sialosyl-Tn and T antigens. Statistical analysis, performed using a Chi-square test, showed significantly lower (P = 0.037) expression of sialosyl-Tn and higher (P = 0.022) expression of T in HNPCC than in sporadic CRC, suggesting a greater presence of beta 1,3 galactosyltransferase activity in HNPCC than in sporadic CRC. We were unable to identify a peculiar phenotype for HNPCC with simultaneous evaluation of reactivity for HB-Tn1, HB-STn1, HB-T1 and ACA; the biological significance of the preferential expression of T antigen in HNPCC remains to be investigated.
Journal of Pediatric Gastroenterology and Nutrition, 1988
ABSTRACT Data on the frequency of regression of Barrett's esophagus after medical... more ABSTRACT Data on the frequency of regression of Barrett's esophagus after medical therapy or antireflux surgery in adult patients are conflicting; these data, with regard to Pediatric age, where Barrett's esophagus is considered rare, are scarce and disappointing after antireflux surgery. We report a 4-month-old infant affected by severe reflux esophagitis who developed a junctional-type Barrett's epithelium. Histochemical procedures to detect mucin pattern were also carried out. The regression of Barrett's esophagus was observed 4 months after antire-flux surgery whereas medical therapy had been unsuccessful. We suggest that esophageal biopsy should also be performed in the presence of severe esophagitis. Longer follow-up observations of other patients may clarify the role of antireflux surgery when Barrett's esophagus complicates gastroesophageal reflux (GER).
1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepato... more 1. Pathology. 1996 Aug;28(3):288. A proposal of additional immunohistochemical markers for hepatoid carcinomas of the foregut. Caruso RA, Tuccari G. Comment on Pathology. 1995 Jul;27(3):277-9. PMID: 8912366 [PubMed - indexed for MEDLINE]. Publication Types: ...
Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This h... more Laurèn's system subdivides gastric cancers into an intestinal type and a diffuse type. This histological classification mirrors histogenetic hypotheses according to which the intestinal-type cancer derives from intestinal metaplasia and dysplasia, while the diffuse-type originates directly from gastric mucosa, with or without a preceding non-metaplastic dysplasia. Studies concerning mucins expression in gastric neoplastic and preneoplastic lesions have provided contradictory data concerning such histogenetic relationships. The aim of the present study was to verify whether a correlation between mucins phenotype and Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided, according to Laurèn's classification, into 27 intestinal-type, 10 diffuse-type and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical expression. Intestinal-type carcinomas displayed a MUC1-positive staining in 23/27 cases and a MUC2-positive immunoreaction in 10/2...
Hepatobiliary & Pancreatic Diseases International, 2015
ABSTRACT BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrate... more ABSTRACT BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic lesions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocytochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions. METHODS: A series of 46 pancreaticobiliary carcinomas with available cell block preparations was submitted to immunocytochemistry against cytokeratins, carcinoembryonic antigen, E-cadherin, CD10 and p53. The sensitivity, specificity, positive and negative predictive values of the cytological smear in the discrimination of malignant lesions were calculated and compared with those of cell block preparation with the immunocytochemical stains against p53 and CD10. RESULTS: According to our findings, the use of cell block preparations together with immunostains against p53 and CD10 allowed to discriminate malignant versus benign specimens with higher sensitivity than the only cytological examination. In detail, CD10 immunostaining was of significant help for the discrimination between cytological contaminants, such as benign gastrointestinal cells, and the neoplastic elements of pancreaticobiliary well differentiated adenocarcinomas. Also, intense nuclear immunoreactivity for p53 was encountered in about 2/3 of the cases and identified pancreatic malignancy with high sensitivity. CONCLUSIONS: We suggest that immunocytochemistry against both CD10 and p53 could be applied case by case, mainly to differentiate gastrointestinal and pancreatic benign cellular contaminants showing hyperplasia or reactive changes from differentiated pancreaticobiliary adenocarcinomas.
Since an aberrant glycosylation associated with abnormal expression of cell surface carbohydrates... more Since an aberrant glycosylation associated with abnormal expression of cell surface carbohydrates has been described in many human tumours, we have investigated the expression of simple mucintype carbohydrate antigens (Tn, sialosyl-Tn and T) in 30 formalin-fixed paraffin-embedded surgical specimens of primary meningiomas, subdivided according to the WHO classification as follows: 18 meningotheliomatous, 7 transitional, 2 angiomatous and 3 anaplastic; in addition, 5 meningeal samples taken at autopsy were tested as control. Specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1, Dako) were utilized with ABC method; the percentage of immunostained cells was graded as follows: O (no staining); 1 (> 0 to 5%); 2 (> 5 to 50%); 3 (> 50%). Tn antigen was not expressed in any case. Sialosyl-Tn antigen was demonstrated only in cases of anaplastic meningiomas (score 1-3). The immunoreactivity for T antigen was found in 2 cases of meningotheliomatous (score 1) and in all the anaplas...
European review for medical and pharmacological sciences, 2012
The odontoameloblastoma (OA), also known as ameloblastic odontoma, is a rare neoplasm of jaws whi... more The odontoameloblastoma (OA), also known as ameloblastic odontoma, is a rare neoplasm of jaws which includes odontogenic ectomesenchyme in addition to odontogenic epithelium that resembles an ameloblastoma both in structure and in behaviour. The exact incidence is difficult to determine. Since 1944, only 24 cases have been reported in English literature which fulfill both histological and clinical features of this lesion. The Authors report a case report of an odontoameloblastoma in a 15-year-old caucasian man treated with a surgical excision. The five years follow-up shows no evidence of recurrence confirming the validity of a conservative surgery with enucleation of OA, followed by periodical clinical and radiographical controls.
The diagnosis of celiac disease (CD) is still mainly based on pathological description. However, ... more The diagnosis of celiac disease (CD) is still mainly based on pathological description. However, these descriptions are often unable to identify latent CD. The aim of this study was to evaluate whether the Marsh-Oberhuber classification and a recently proposed classification may help to identify patients with latent CD. Biopsy samples from twelve patients with latent CD (age range 3-32 years) defined as having normal duodenal mucosa when ingesting a free diet, and subsequently developing severe villous atrophy, were retrospectively reviewed in blind according to the Marsh-Oberhuber classification and the new grading system. In 67% of patients the Marsh-Oberhuber and the new classification could have yielded a diagnosis of CD soon after the first biopsy (3a-3c score when reviewed according to this classification, and B2 score when reviewed according to the new grading system), thereby avoiding further (up to two more in four cases) unnecessary endoscopic procedures. Both the Marsh-Ob...
Using a sequential method for the simultaneous demonstration of lysozyme and mucins, the possible... more Using a sequential method for the simultaneous demonstration of lysozyme and mucins, the possible existence of a transitional cell intermediate in form between Paneth and goblet cells has been investigated in childhood coeliac disease. Mixed staining for both mucins and lysozyme has not been encountered within intestinal cells of affected mucosae and controls.
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Papers by G. Tuccari