Bone sialoprotein is predictive of bone metastases in resectable non small cell lung carcinoma: A case–control study and prevalence data

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Detection and characterization of classical and "uncommon" exon 19 Epidermal Growth Factor Receptor mutations in lung cancer by pyrosequencing

BACKGROUND: The management of advanced stage non-small cell lung cancer is increasingly based on diagnostic and predictive analyses performed mostly on limited amounts of tumor tissue. The evaluation of Epidermal Growth Factor Receptor (EGFR) mutations have emerged as the strongest predictor of response to EGFR-tyrosine kinase inhibitors mainly in patients with adenocarcinoma. Several EGFR mutation detection techniques are available, having both sensitivity and specificity issues, being the Sanger sequencing technique the reference standard, with the limitation of a relatively high amount of mutated cells needed for the analysis. METHODS: A novel nucleotide dispensation order for pyrosequencing was established allowing the identification and characterization of EGFR mutation not definable with commercially and clinically approved kits, and validated in a consecutive series of 321 lung cancer patients (246 biopsies or cytology samples and 75 surgical specimens). RESULTS: 61/321 (19%) mutated cases were detected, 17 (27.9%) in exon 21 and 44 (72.1%) in exon 19, these latter corresponding to 32/44 (72.7%) classical and 12/44 (27.3%) uncommon mutations. Furthermore, a novel, never reported, point mutation, was found, which determined a premature stop codon in the aminoacidic sequence that resulted in a truncated protein in the tyrosine kinase domain, thus impairing the inhibitory effect of specific therapy. CONCLUSIONS: The novel dispensation order allows to detect and characterize both classical and uncommon EGFR mutations. Although several phase III studies in genotypically defined groups of patients are already available, further prospective studies assessing the role of uncommon EGFR mutations are warranted

Management of neuroendocrine differentiated breast carcinoma

In neuroendocrine differentiated breast cancer, the coexistence of both neuroendocrine and exocrine components may raise some uncertainty about the best clinical approach to adopt. We describe the case of a patient with neuroendocrine differentiated breast carcinoma with lung metastases, who experienced a partial response after epirubicin chemotherapy. During subsequent maintenance hormone therapy with letrozole, plasma chromogranin A was consistently elevated even though CT showed disease stabilization. The patient was scheduled for surgery and radical resection was performed. She is still alive and disease free after over 37 months. Anthracyclines are effective in the treatment of neuroendocrine differentiated breast carcinoma. Surgical resection of metastatic lesions can lead to a durable disease-free status. Serial evaluation of circulating chromogranin A is useful in the follow-up of these patients