Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features.

AIMS: Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information. METHODS AND RESULTS: Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway. CONCLUSIONS: These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.

[Slow-resolution pneumonia: radiologic and tomodensitometric features]. / Polmoniti con risoluzione lenta: aspetti radiologici e tomodensitometrici.

To assess the radiologic findings of unresolving pneumonias (radiologic signs not normalized at the end of the fourth week of antibiotic therapy), the radiologic (192) and CT examinations (33) of 50 patients were reviewed, for a total of 64 pulmonary parenchymal lesions. These lesions presented as masses (3; 4.6%), parenchymal thickenings with aerial bronchogram (41; 63.7%), sometimes escavated (4; 10%), alveolar ground glass alterations (4; 6.2%), more frequent on the right side (49; 73%), mostly in the upper lobe (21; 32.8%). Pleural effusion was demonstrated in 16 patients (32%) and lymphadenopathies were shown in 8 patients (8%). When possible, the responsible germ was isolated with microbiological expectoration test (14; 35.3%), bronchoscopy associated with bronchoalveolar lavage (7; 37.5%) and needle biopsy in the mass (2; 5%). The germs were Candida (9), haemophilus influentiae (1), Klebsiella (1), pneumococcus (1), Pseudomonas (3), Staphylococcus aureus (4), streptococcus alpha hemoliticus (6). There are no typical radiologic and CT findings for the described lesions in different-patients and different germs can produce the same changes. Therefore, pulmonary inflammations must be followed to their complete resolution, to rule out the chance of a neoplastic process (obstructive pneumonia). The first radiologic control must be made at least 15 days after the beginning of therapy for the anatomo-pathologic processes of recovery to show radiographically. CT can be fundamental in the differential diagnosis with neoplasm, in unresolving pneumonia, to study the tracheobronchial tree, to study lymphadenopathies and to guide needle biopsy.

[Thoracic radiography and high resolution computerized tomography in the diagnosis of pulmonary disorders caused by amiodarone]. / Radiografia del torace e Tomografia computerizzata ad alta risoluzione nella diagnosi delle alterazioni polmonari da amiodarone.

To assess the radiographic patterns of amiodarone-induced pulmonary toxicity, the chest films (32) and HRCT scans (16) were reviewed of 14 patients into amiodarone protocols for 3 months to 6.5 years (average: 40.5 months). All patients were symptomatic and presented with shortness of breath, a general malaise, a fever. The radiographic findings included: intersurface signs, defined as irregular interfaces between parenchyma, bronchi, vessels and visceral pleura, indicating interstitial abnormalities (HRCT: 8 = 50%); septal thickening (Kerley's lines) (chest film: 32 = 100%; HRCT: 6 = 37%); reticular opacities (chest film: 24 = 75%; HRCT: 6 = 37%); peribronchial cuffing (chest film: 2 = 6%; HRCT: 0); interstitial nodules (chest film: 12 = 37%; HRCT: 4 = 25%); alveolar nodules (chest film: 16 = 50%; HRCT: 12 = 75%); consolidations (chest film: 20 = 62%; HRCT: 12 = 75%); parenchymal masses (chest film: 2 = 6%; HRCT: 2 = 12%); fibrosis (chest film: 24 = 75%; HRCT: 16 = 100%); reduced lung volume (chest film: 14 = 43%; HRCT: 4 = 25%); pleural effusion and/or thickening (chest film: 4 = 12%; HRCT: 4 = 25%). The lesions were always localized in the lower lobes and often also in the upper lobes (chest film: 12 = 37%; HRCT: 14 = 87%); in the latter site the lesions were smaller. HRCT showed the peripheral site of the lesions. Amiodarone discontinuation and corticosteroids administration improved the radiographic patterns in 2 patients and attenuated the symptoms, with disappearance of alveolar nodules, in 11 patients. In contrast, clinical symptoms progressed and the radiographic pattern worsened in one patient. Both chest films (Kerley's lines, reticular, interstitial and alveolar opacities without cuffing and pleural effusion or clear fibrosis) and HRCT (fibrosis associated with alveolar opacities) showed sufficiently typical patterns of amiodarone-induced pulmonary toxicity, especially when associated with pleural thickening.

[Radiography and computerized tomography of the thorax in lung small cell tumors. Diagnostic possibilities]. / Radiografia e tomografia computerizzata del torace nel tumore a piccole cellule. Possibilità diagnostiche.

Small cell lung cancer (SCLC) is a highly malignant tumor which is nearly always metastatic at diagnosis and generally staged as a localized or diffuse disease. The authors compared the capabilities and the advantages of CT with those of chest films in the diagnosis, staging and follow-up of this type of cancer in 54 patients (52 men and 2 women, mean age: 62 years, range: 45 to 79 years). All the patients were submitted to the same examinations 3 months (18 patients), 6 months (6 patients), 9 months (6 patients) and 12 months (2 patients) after radiochemotherapy. Median survival time was 13 months (range: 6-20 months). On staging, radiography showed mediastinal masses (63%), bronchial narrowing (57%), hilar masses (45%), atelectasis (37%), pleural effusion (29%), pericardial thickening and/or effusion (22%), multiple (20%) or single (16%) peripheral masses and tracheal narrowing (2%). CT was more sensitive, chiefly in depicting mediastinal masses (34 cases demonstrated by CT vs 12 by chest films), bronchial narrowing (38 vs 0) and pericardial involvement (12 vs 0); after CT, 12 patients with localized disease on chest films were diagnosed as having diffuse disease. Complete response after therapy, i.e., the total disappearance of all signs and symptoms of disease for 30 days at least, was depicted by CT in 16 patients and by chest films in 9 patients. Partial response-i.e., disease decrease by 50% or more, with no new lesions, for 30 days at least--was depicted by CT in 16 patients and by chest films in 4 patients. Finally, no response or disease progression was depicted by CT in 10 patients and by chest films in 9 patients. To conclude, the presence of mediastinal and hilar masses, with bronchial narrowing, atelectasis, pleural/pericardial involvement, sometimes with a peripheral mass, are strongly suggestive of small cell lung cancer. CT was more sensitive than chest films in the staging of localized and diffuse disease, but it failed nevertheless to improve significantly the diagnosis, prognosis and follow-up of SCLC relative to chest films (p = 0.34).

[Pulmonary tuberculosis in non-immunocompromised patients. Current radiologic features]. / La tubercolosi polmonare nei pazienti non immunodepressi. Attuali aspetti radiologici.

Sixty-four non-immunocompromised and adult patients with proved tuberculosis were examined. Twenty-three of them had bacteriologic confirmation with sputum examination, 7 with biopsy, 8 with bronchoscopy and bronchial lavage, 3 with pleural effusion examination and 3 with specific ex-juvantibus therapy. Fifteen patients had positive Mantoux skin tests. Thirty-nine patients had primary and 25 postprimary tuberculosis. All patients underwent chest radiography and 37 underwent also CT scans of the chest. The radiographic findings in primary tuberculosis were: 33 parenchymal consolidation patterns (in 24 patients), more frequent in the upper (20/33) than in the lower (13/33) lobes, with cavitations in 16 cases; 2 miliary patterns; 4 atelectasis cases; 4 intrathoracic adenopathies and 11 pleural effusions. The radiographic findings in postprimary tuberculosis were: 32 parenchymal consolidation patterns (in 19 patients), more frequent in the upper (27/32) than in the lower (5/32) lobes, with cavitations in 7 cases; 2 tuberculomas; 1 miliary pattern; 1 atelectasis; 5 pleural effusions and 1 pericardial effusion. Thus, we can conclude that in our series both primary and postprimary tuberculosis appear mostly as upper lobe consolidation, with cavitations especially in the primary form, often with pleural effusion and sometimes with intrathoracic adenopathies. Primary tuberculosis is most frequent in adult men. Finally, lower lobe consolidations or less typical radiographic patterns are observed, e.g., atelectasis, adenopathies or pleural effusion with no parenchymal changes, which can mimic other diseases and thus delay the diagnosis.