Immunophenotypic profile of tumor buds in breast cancer.

BACKGROUND: Tumor buds are associated with lympho-vascular invasion and lymph node metastases leading to the assumption that they are involved in the early metastatic process. Hence, it would be important to know if tumor buds can be targeted with the most widely used targeted therapies in breast cancer (BC) and if changes in hormone and Her2 status occur. The aim of this study was to answer these questions by determining whether hormone receptor (HR) and Her2 status are expressed in the tumor buds of a large cohort of BCs. DESIGN: We constructed a tumor bud next-generation tissue microarray (ngTMA) consisting of n = 199 BCs of non-special type. Generally, two 1 mm punches were taken from the tumor bud areas in the periphery (PTB) and within the tumor center (ITB). HR and Her2 status was assessed using immunohistochemistry and fluorescence in situ hybridization, respectively. HR status was positive if ≥1% of tumor bud cells were positive. Her2 status was considered positive if bud cells showed strong complete membranous Her2 over-expression or Her2 amplification. RESULTS: Most tumor buds were positive for estrogen (ER) (PTB: 86%; ITB: 88.3) and progesterone receptor (PgR) (PTB: 72%; ITB: 72.8%) and Her2 was positive in: PTB 11.5% and ITB 11%. A difference between the main tumor mass and tumor buds (PTB and ITB) was seen for PgR in 3.5% of cases (n = 7). No differences were seen for ER and Her2 between tumor buds and main tumor mass. CONCLUSION: Most tumor buds (96.5%) share the same HR and Her2 expression profile of the main tumor mass, implying that tumor buds relay on the same pathways as the main tumor mass and might be equally responsive to targeted therapies.

Prognostic role of FGFR1 amplification in early-stage non-small cell lung cancer.

BACKGROUND: Recently, fibroblast growth factor receptor 1 (FGFR1) was discovered in squamous cell carcinomas (SCC) of the lung with FGFR1 amplification described as a promising predictive marker for anti-FGFR inhibitor treatment. Only few data are available regarding prevalence, prognostic significance and clinico-pathological characteristics of FGFR1-amplified and early-stage non-small cell lung carcinomas (NSCLC). We therefore investigated the FGFR1 gene status in a large number of well-characterised early-stage NSCLC. METHODS: FGFR1 gene status was evaluated using a commercially available fluorescent in situ hybridisation (FISH) probe on a tissue microarray (TMA). This TMA harbours 329 resected, formalin-fixed and paraffin-embedded, nodal-negative NSCLC with a UICC stage I-II. The FISH results were correlated with clinico-pathological features and overall survival (OS). RESULTS: The prevalence of an FGFR1 amplification was 12.5% (41/329) and was significantly (P<0.0001) higher in squamous cell carcinoma (SCC) (20.7%) than in adenocarcinoma (2.2%) and large cell carcinoma (13%). Multivariate analysis revealed significantly (P=0.0367) worse 5-year OS in patients with an FGFR1-amplified NSCLC. CONCLUSIONS: FGFR1 amplification is common in early-stage SCC of the lung and is an independent and adverse prognostic marker. Its potential role as a predictive marker for targeted therapies or adjuvant treatment needs further investigation.

A rare case of a large spinal meningioma with mediastinal extension and malignant behavior classified histologically as benign.

AIM: To report a rare case of a spinal WHO grade I meningioma extending through intervertebral foramina C7 to D4 with an extensive mediastinal mass and infiltration of the vertebrae, and to discuss the malignant behavior of a tumor classified as benign. METHODS: (Clinical Presentation, Histology, and Imaging): A 54-year-old man suffered from increasing lower back pain with gait difficulties, weakness and numbness of the lower extremities, as well as urge incontinence. CT scan of the thorax and MRI scan of the spine revealed a large prevertebral tumor, which extended to the spinal canal and caused compression of the spinal cord at the levels of C7 to D4 leading to myelopathy with hyperintense signal alteration on T2-weighted MRI images. The signal constellation (T1 with and without contrast, T2, TIR) was highly suspicious for infiltration of vertebrae C7 to D5. Somatostatin receptor SPECT/CT with (111)In-DTPA-D: -Phe-1-octreotide detected a somatostatin receptor-positive mediastinal tumor with infiltration of multiple vertebrae, dura, and intervertebral foramina C7-D4, partially with Krenning score >2. Percutaneous biopsies of the mediastinal mass led to histopathological findings of WHO grade I meningioma of meningothelial subtype. RESULTS: (Therapy): C7 to D4 laminoplasty was performed, and the intraspinal, extradural part of the tumor was microsurgically removed. Postoperative stereotactic radiation therapy was done using the volumetric modulated arc therapy (VMAT) technique (RapidArc). No PRRNT with (90)Y-DOTA-TOC was done. CONCLUSIONS: Due to the rare incidence and complex presentation of this disease not amenable to complete surgical resection, an individualized treatment approach should be worked out interdisciplinarily. The treatment approach should be based not only on histology but also on clinical and imaging findings. Close clinical and radiological follow-up may be mandatory even for benign tumors.