RESUMO
BACKGROUND: This study aims to investigate the frequency, distribution, and morphological/immunohistochemical features of epidermal growth factor receptor mutations and to examine the possible relationship between the material type and technical success of mutation analysis in Turkish population with non-small cell lung cancer. METHODS: Between September 2012 and December 2015, a total of 499 consecutive, treatment-naïve patients (437 males, 163 females; mean age 61 years; range, 30 to 84 years) with primary or metastatic non-small cell lung cancer who underwent epidermal growth factor receptor mutation testing using Sanger sequencing method were retrospectively analyzed. Archival records and hematoxylin-eosine and immunohistochemically stained sections were re-examined. The thyroid transcription factor-1 and napsin A immunohistochemical stains were performed on tissue array blocks. RESULTS: Seventy-five mutations were detected in 70 patients (14%). The success rate of testing and intact deoxyribonucleic acid fragment length were significantly higher in the cytological material, compared to tissue specimens (p<0.001). The mutation rate in adenocarcinomas was 33.9% for women and 9.4% for men. The most common mutation was L746-E750del in exon 19 (29.3%), followed by the L858R mutation in exon 21 (28%). The mutation rate was the highest in micropapillary (40%) and lowest in solid (5.4%) adenocarcinomas. All epidermal growth factor receptor mutations, except for one, were positive for the thyroid transcription factor-1. The single nucleotide polymorphism Q787Q in exon 20 was observed in 79.6% of patients. CONCLUSION: The frequency and distribution of epidermal growth factor receptor mutations in the Turkish patients with non-small cell lung cancer are similar to the European populations. These results also demonstrate that cytological materials are highly reliable for epidermal growth factor receptor mutation testing, and the probability of detection of wild-type epidermal growth factor receptor is low in cases of thyroid transcription factor-1 negativity.
RESUMO
Our aim in this study was to describe the clinical, morphological, and molecular profile of gastrointestinal stromal tumor (GIST) metastatic to bone. We analyzed the morphological, phenotypic, and molecular characteristics of seven cases, and in addition reviewed 17 cases from literature. Sequence analysis of KIT and PDGFRA genes was possible for six cases. For the GIST cases with bone metastasis, the most common primaries were small intestine (29%), stomach (25%), and rectum (21%). Sites of bone metastases were vertebrae (11), pelvis (8), femur (8), ribs (6), humerus (5), skull (3), scapula (1), and mandible (1). The size ranged from 1.5 to 13 cm (median, 3.8 cm). Bone metastases without involvement of any other organ were seen in 17% of the cases and were solitary in 14 (58%). Adjacent soft tissue involvement was present in nearly half of the patients. Bone metastasis was either manifest at the time of diagnosis (28%) or occurred after a mean period of 4.7 years (3 months-20 years). Morphologically, neoplastic cells were spindle in 67%, epithelioid in 13%, and mixed epithelioid and spindle in 20%. CD117, DOG1, and CD34 were positive in 88, 86, and 85% of the cases, respectively. KIT Exon 11 mutations were the most frequent gene alteration (78%), followed by KIT Exon 13 mutations. Of 17 of the cases with available follow-up information, 7 (41%) patients developed bone metastasis under imatinib therapy. Five patients (29%) died of disease within a mean of 17 months. Bone metastases from GIST are usually found in patients with advanced disease and typically present as lytic masses with occasional soft tissue involvement. We could not identify any KIT or PDGFRA alterations predisposing to bone metastasis.