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Biomedical subjects

Giulio Rossi

Publications and source records attributed to Giulio Rossi.

At least 19 recordsLinked to original sources
PubMed2006

Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients.

Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Bronchial typical carcinoid tumors.

The current WHO classification of lung tumors recognizes bronchial typical carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites. Symptoms are usually related to local compression and obstruction of the bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome, Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy are useful in the preoperative staging. Only selected cases can be treated endoscopically with laser resection. The complete surgical resection remains the only therapy with curative intent in the majority of patients. Parenchyma-sparing resections are indicated whenever possible. Overall survival after surgery is excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status and type of resection seem not to affect prognosis. Local relapse can be treated successfully with surgery, whereas distant metastases have a poor prognosis even after chemotherapy.

Bronchial Neoplasms↗
PubMed2006

Exclusive intrapulmonary lepidic growth of a malignant pleural mesothelioma presenting with pneumothorax and involving the peritoneum.

We report a rare case of malignant pleural mesothelioma presenting clinically with pneumothorax and histologically with an exclusive intrapulmonary lepidic growth. Neither intrathoracic nodules nor pleural thickening were found. The patient subsequently experienced acute abdominal pain with peritonitis and intestinal occlusion by peritoneal mesothelioma. The morphologic clues leading to the correct diagnosis of mesothelioma with prominent intrapulmonary growth are briefly discussed.

Biomarkers, Tumor↗
PubMed2006

Pleural malignant solitary fibrous tumor with sarcomatous overgrowth showing PDGFRbeta mutation.

Pleural malignant solitary fibrous tumors (SFTs) are uncommon, and little is known about their histogenesis and molecular features. We report a case of pleural SFT with sarcomatous overgrowth that showed expression for PDGFRbeta and a missense mutation on exon 18 of the PDGFRbeta gene. The involvement of the PDGFRbeta gene in SFT is compatible with a pericytic derivation, also supporting a possible role of this tyrosine kinase in malignant transformation and in the adoption of novel molecular therapies.

Aged↗
PubMed2006

Papillary fibroelastoma of the right atrium as an unusual source of recurrent pulmonary embolism.

Papillary fibroelastoma is the most common primary tumour of cardiac valves, with the potential for embolic events and obstructive effects. Location in non-valvular endocardium is extremely rare. Transthoracic and transoesophageal echocardiography have greatly increased the ability to make the diagnosis of these surgically treatable tumours in a timely fashion. We report the case of a 70-year-old woman with symptoms and ventilation-perfusion scan evidence of pulmonary embolization from a papillary fibroelastoma of the right atrium. Initial transthoracic echocardiography failed to identify the tumour, whereas transoesophageal echocardiography demonstrated a mobile echodense mass attached to the right atrial free wall. After surgical excision, histopathology revealed papillary fibroelastoma. The epidemiology, aetiology, localization, macroscopy, histopathology, immunohistochemistry, clinical presentation, diagnosis and management of cardiac papillary fibroelastoma are reviewed. The case is unusual with respect to the site of origin of the papillary fibroelastoma as well as its clinical presentation, which is clearly related to pulmonary embolization.

Aged↗
PubMed2005

Role of chemotherapy and the receptor tyrosine kinases KIT, PDGFRalpha, PDGFRbeta, and Met in large-cell neuroendocrine carcinoma of the lung.

PURPOSE: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets. PATIENTS AND METHODS: We reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRalpha, PDGFRbeta, and Met. RESULTS: LCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRalpha in 60.2%, PDGFRbeta in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (> or = 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001). CONCLUSION: Pulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide-based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRalpha, PDGFRbeta, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.

Adult↗
PubMed2005

Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases.

OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients as regard to prognosis and treatment. Indication and timing of surgery remain controversial. The present study investigates the prognostic factors, in order to identify homogenous subgroups of patients. METHODS: Histologically proven N2-NSCLC patients, who underwent a complete surgical resection were retrospectively reviewed. Clinical and pathological features were reported and analyzed, and survival study was performed. RESULTS: One hundred eighty-three patients were analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and 20%, with a median survival time of 24 months. Univariate analysis showed a significant better prognosis for: incidental N2 respect to clinical N2 (5-years 35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5-years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe tumors with superior mediastinal nodes and left upper lobe tumors with aortic nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8 and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage respect to continuous lymphatic spread. N2 clinical status, the number of levels involved and the two specific patterns of lymphatic spread resulted significant prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status, number of lymph nodes levels involved and specific patterns of lymphatic spread identify homogenous subgroups of patients that can be proposed for different therapeutic strategies.

Adult↗
PubMed2005

Does HPV play a role in the etiopathogenesis of ameloblastoma? An immunohistochemical, in situ hybridization and polymerase chain reaction study of 18 cases using laser capture microdissection.

Ameloblastomas are epithelial tumors of odontogenic origin, biologically characterized by local recurrence. Among different etiologic factors, HPV infection has been recently postulated to be somehow involved in ameloblastoma etiopathogenesis. To address this issue, we studied 18 ameloblastomas by means of immunohistochemistry, in situ hybridization (conventional and amplified), polymerase chain reaction and nested-polymerase chain reaction analyses using laser capture microdissection in order to detect the occurrence of HPV in this setting. No evidence of HPV infection was detected by morphological examination, immunohistochemistry, in situ hybridization and conventional polymerase chain reaction, while nested-polymerase chain reaction showed a weak positive band in two cases. However, the subsequent restriction enzyme analysis carried out from the nested-polymerase chain reaction amplification products of these two samples excluded the presence of HPV subtypes 16, 18, 31, 33, 35, 52, and 58. The search for HPV 6 and 11 in the same specimens was also negative. In conclusion, our data do not support an etiopathogenetic evidence for HPV in ameloblastoma.

Adolescent↗
PubMed2005

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer.

Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P=0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P=0.04 by log-rank test) and disease progression (P=0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.

Adult↗
PubMed2004

Placental transmogrification of the lung: clinicopathologic, immunohistochemical and molecular study of two cases, with particular emphasis on the interstitial clear cells.

Two cases of placental transmogrification of the lung are reported. The lesions presented in the left lung, in one case as a giant bulla of the upper lobe and in the other as a cystic nodule of the lower lobe. A segmentectomy was performed in both cases, and the patients were alive and well 5 years and 2 months after surgery, respectively. In our opinion, pulmonary placental transmogrification is not a variant of emphysema, as generally considered, but rather probably represents a benign proliferation of immature interstitial clear cells with secondary cystic change. This report presents a histological, immunohistochemical, ultrastructural and molecular study of these peculiar cells, together with a review of the literature.

Adult↗
PubMed2004

The prognostic role of c-kit protein expression in resected large cell neuroendocrine carcinoma of the lung.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor of the lung that shares some clinicopathologic and molecular features with small cell lung carcinoma (SCLC). Optimal treatment has not yet been standardized and significant prognostic factors are lacking. Because c-kit protein overexpression has been recently reported as a negative prognostic factor in SCLC we investigated its expression and prognostic value in a series of LCNEC. METHODS: Resected LCNEC fulfilling the morphologic criteria of the 1999 World Health Organization classification of lung tumors and showing neuroendocrine differentiation by appropriate immunohistochemical markers were retrospectively reviewed. Immunostaining for c-kit protein expression was performed using the polyclonal antibody CD117. Clinical and pathologic characteristic were reported and analyzed and a survival study was performed. RESULTS: Thirty-three patients underwent radical resection. Thirty-one were male (94%) and 32 were smokers (97%). Ten (30.3%), 11 (33.3%), 5 (15.2%), and 7 (21.2%) were at stage IA, IB, IIB, and IIIA respectively. Overall 1-, 3-, and 5-year survival rates were respectively 79%, 58%, and 51%. Survival analysis showed no differences for any of the clinicopathological features except for CD117 immunostaining: 1-year and 3-year survival rates were respectively 91% and 82% for CD117-negative LCNEC, and 72% and 44% for CD117-positive ones (p = 0.046). Positivity of CD117 was significantly related to recurrence rate: 60% versus 23% for CD117 positive and negative LCNEC respectively (p = 0.037). CONCLUSIONS: Radical resection of large cell neuroendocrine carcinoma achieves poor outcomes. The c-kit protein is frequently expressed in this neoplasia and its expression represents a negative prognostic factor. This immunohistochemical marker may represent the basic rationale to select LCNEC for novel targeted therapy.

Adult↗
PubMed2004

Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression.

Herein we describe the clinicopathologic and immunohistochemical features of 13 primary mucinous (colloid) carcinomas (MCs) of the lung, an uncommon and controversial tumor. The patients, 7 males and 6 females, ranged in age from 50 to 79 years (mean, 64.5 years). All the tumors presented as a peripheral solitary nodule with gelatinous cut-surface and well circumscribed but lacking a complete fibrous wall. The size ranged from 1 to 5.5 cm. Microscopically, they consisted of neoplastic elements floating in large mucin pools and focally lining the alveolar spaces. Eleven cases were predominantly composed of tall, columnar goblet cells (goblet cell-type MC), while 2 consisted of signet-ring tumor cells (signet-ring cell-type MC). Five tumors were incidentally discovered by chest radiographs, while the others were symptomatic. All patients underwent complete surgical resection (six lobectomies and seven wedge resections). Postoperative chemotherapy was performed in 3 cases. Overall, the median follow-up was 26 months (mean 33 months; range 9-95 months). All patients with goblet cell-type MC were alive and well, while the 2 patients with signet-ring cell-type MC died of disease. Immunohistochemically, all the 11 goblet cell-type MCs were strongly stained with CDX-2 and MUC2, 8 reacted with TTF-1, 6 with cytokeratin 20 (CK20), 9 with cytokeratin 7 (CK7), and 2 with MUC-5AC. Conversely, the two signet-ring cell-type MCs were stained with TTF-1, CK7, and MUC5AC but were negative for CDX-2, MUC2, and CK20. Surfactant apoprotein-A (SP-A) was positive in four goblet cell-type and one signet-ring cell-type MC. When compared with 10 mucinous bronchioloalveolar carcinomas (m-BAC), the latter reacted with CK7, CK20, MUC5AC, TTF-1, SP-A, CDX-2, and MUC2 in 100%, 90%, 100%, 30%, 10%, 0%, and 0% of the cases, respectively. In summary, MC of the lung represents an entity with two distinct clinicopathologic and immunophenotypic variants: 1) the goblet cell-type, presenting a more indolent clinical behavior and frequently co-expressing markers of intestinal and pulmonary differentiation; and 2) the more aggressive signet-ring cell-type, which retains only markers of pulmonary origin. On morphologic and immunohistochemical grounds, MCs are easily distinguishable from m-BAC. Since goblet cell-type MC strongly stains with CDX2, MUC2, and CK20, differential diagnosis with metastatic colorectal carcinoma is very challenging and requires appropriate clinical correlation.

Adenocarcinoma, Mucinous↗
PubMed2004

Primary mixed adenocarcinoma and small cell carcinoma of the appendix: a clinicopathologic, immunohistochemical, and molecular study of a hitherto unreported tumor.

Appendiceal carcinoids range from well-differentiated endocrine tumor to well-differentiated endocrine carcinoma, while poorly differentiated (small cell) carcinoma has not been described in this site. We report herein a case of mixed intestinal-type adenocarcinoma associated with a small cell carcinoma arisen in a 35-year-old woman and clinically presenting as an appendiceal abscess. The resected tumor histologically appeared as a biphasic lesion composed of a nonmucinous adenocarcinoma closely juxtaposed with a poorly differentiated (small cell) endocrine carcinoma. The subsequent right hemicolectomy was unremarkable, but one pericolic lymph node showed a metastatic deposit consisting of the adenocarcinoma only. The patient thus underwent a chemotherapeutic protocol for colorectal cancer, and she is alive and well at the 65-month follow-up. Immunohistochemically, the adenocarcinoma strongly stained for cytokeratin 20 and carcinoembryonic antigen, while the endocrine component displayed a dot-like positivity for pan-cytokeratins and chromogranin. Of note, both components did not stain with CDX2 and p53. At genotypic analysis by microsatellite instability, both components shared many microsatellite alterations as well as a normal p53 gene setup, although small cell carcinoma harbored additional alterations. Clinical and molecular findings led us to consider this lesion as a clonal tumor in which the endocrine component seems to derive from a progressive differentiation of the adenocarcinoma following a glandular-to-endocrine sequence.

Adenocarcinoma↗