Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

BACKGROUND: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT. MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features. RESULTS: Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E). CONCLUSIONS: All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.

Endobronchial valve for secondary pneumothorax in a severe emphysema patient.

Secondary pneumothorax represents a challenging problem in patients with chronic obstructive pulmonary disease, due to their compromised health status. In this case, an endobronchial one-way valve was inserted in the left lower lobe by flexible bronchoscopy, resulting in a complete resolution of air leak and lung reexpansion. Endobronchial valve could represent a new option for the management of persistent air leak in patients not suitable for surgical procedures.

Evaluation of the circulating glycoprotein CA549 in mammary cancer and other malignancies.

A prospective study was carried out on a recent marker for breast cancer, CA549, a mucine-like acid glycoprotein present in the fat membranes of human milk. Fifty healthy control subjects and 91 with benign conditions, 103 mammary cancer patients and 256 patients with other types of malignancy were studied. For comparison, CEA and CA15-3 were also investigated. The CA549 cutoff was 11 U/ml. In breast cancer the marker was below the cutoff in 9 cases (92.8%); in malignancies other than breast cancer it was above the cutoff in 5 to 50% of patients. In breast cancer it was raised in 83.3% of cases (CA15-3 showed 82.9% and CEA 50%). In breast cancer after radical surgery, CA549 was normal in patients who were in TNM stage I but above the cutoff in 57.1% of those at more advanced stages. The follow-up study is ongoing among these patients. In all the study conditions, CA549 favorably compared to CA15-3 values, with sensitivity and specificity greater than CEA.

[Excessive prolactinemic response to sulpiride in patients with mild essential hypertension. Index of diminished hypothalamic dopaminergic activity]. / Eccessiva risposta prolattinemica alla sulpiride in pazienti con ipertensione essenziale lieve. Indice di diminuita attività dopaminergica ipotalamica.

Plasma prolactin concentrations and prolactinaemic response to sulpiride, a prolactin releaser with pituitary dopamine receptor blocking activity, were examined in 16 subjects with mild essential hypertension and in 20 patients with long-sustained essential hypertension. When compared with 16 normotensive controls only the former showed raised plasma renin activity (P < 0.001) and higher plasma prolactin levels either after two-hour ambulation (P < 0.05) or at supine rest (P < 0.05). The average of maximal sulpiride-induced prolactin values was 157 +/- 53 ng/ml (mean +/- SD) in the mild hypertensive, significantly different from 60.2 +/- 21.4 ng/ml (mean +/- SD) as resulted in the controls (P < 0.001). In contrast, patients with sustained hypertension had a mean level of 60.2 +/- 21.4 ng/ml (mean +/- SD), indifferent from the one of the normal volunteers. It is suggested that the excessive prolactinaemic response to sulpiride detected in patients with mild hypertension reflects a reduced hypothalamic dopaminergic activity and that such an alteration may assume some pathogenetic relevance in the natural history of essential hypertension. Further, in the mild hypertensive a positive prolactin-renin correlation was found (r = + 0.76; P < 0.01), so suggesting that in these patients a peripheral sympathetic overactivity is associated to an impaired central dopamine control. The individuation of such cases may be important since they could benefit by dopamine agonists as L-dopa and bromocriptine.