The aim of this study was to compare lymphatic drainage patterns detected with fluorescent dye indocyanine green (ICG) with the lymphatic drainage patterns detected with radiotracer ...(99m)Tc-nanocolloid in dynamic sentinel node biopsy (DSNB) procedures.
Fourteen patients with penile cancer and no palpable lymph nodes were included prospectively for DSNB. First, on the day of surgery (99m)Tc-nanocolloid was injected at the lesion site. Then, single photon emission computed tomography (SPECT) lymphoscintigraphy was performed. ICG was injected in the same manner as the radiotracer just before the surgery. In all cases partial penectomy and DSNB were performed. Sentinel lymph nodes (SLNs) were localized intraoperatively using the gamma-ray detection probe for radiocolloid and near infrared fluorescence (NIRF) camera for ICG.
Transcutaneously, lymphatic nodes were identified in all 14 patients using the gamma probe and in 10 patients using the NIRF camera. After skin incision, fluorescent nodes were observed using the NIRF camera in the remaining 4 patients. The examination led to identification of 32 SLNs in total using technetium and ICG and additionally 3 more nodes visible only using ICG. All SLNs found using SPECT were also fluorescent. In 3 patients ICG enabled only approximate localization of the SLNs. Of 35 SLNs, 30 were negative and 4 were positive for metastasis.
Our analysis of the effectiveness of ICG compared with radiocolloid in the DSNB for penile cancer indicates that they are comparable with some specific advantages and disadvantages. These findings must be studied further in a larger group of patients.
Losses in the succinate dehydrogenase (SDH) complex characterize 20% to 30% of extra-adrenal paragangliomas and 7% to 8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as ...lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%), including a patient with an SDHB-deficient GIST. Histologically, the SDHB-negative renal carcinomas varied. There was 1 clear cell carcinoma with a high nuclear grade, 1 papillary carcinoma type 2, 1 unclassified carcinoma with a glandular pattern, and 1 oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, 1 in the retroperitoneal lymph nodes). There were no cases with SDHB loss among 64 renal oncocytomas. SDHB losses were not seen in other carcinomas, except in 1 prostatic adenocarcinoma (1/57), 1 lymphoepithelial carcinoma of the stomach, and 1 (1/40) seminoma. On the basis of this study, SDHB losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study.
ALK receptor tyrosine kinase (ALK) aberrations have an established role in pathogenesis of many neoplasms, but their clinical significance in high grade serous ovarian carcinoma (HGSOC) is unclear.
...To analyse the frequency of ALK overexpression, molecular abnormalities of ALK, and their impact on the progression-free survival (PFS) and overall survival (OS) in HGSOC.
Protein expression was examined by immunohistochemistry (IHC) using three different clones of anti-ALK antibody. The presence of translocations was analysed using fluorescent in situ hybridization. Next-generation sequencing was used for studying the copy number variation, as well as point mutation and translocations involving other commonly rearranged genes.
ALK overexpression was demonstrated in up to 52% of tumours, whereas ALK copy gains in 8.2%, with no clear impact on survival. ALK point mutations were identified in 13 tumours (8.9%), with 3 belonging to the class IV showing significantly better OS. A trend suggesting better PFS was also noticed in these cases. Additionally, three gene fusions were found: ERBB2-GRB7, PRKCA-BRCA1 and SND1-BRAF, none of which has been previously described in HGSOC.
HGSOC harbouring activating ALK mutations might be associated with a better survival, while ALK overexpression and ALK amplification does not impact the prognosis.
Prior studies have demonstrated an association between excision repair cross-complementation group 1 (ERCC1) expression level and outcomes in patients with advanced non-small cell lung cancer (NSCLC) ...treated with platinum-based chemotherapy. The aim of this study was to assess the impact of ERCC1 on survival for patients with stage IIIB/IV non-squamous NSCLC (NS-NSCLC) enrolled in the INNOVATIONS trial, thus receiving as treatment either erlotinib/bevacizumab (EB) or cisplatin/gemcitabine/bevacizumab (PGB). We retrospectively analyzed tumor tissue of 72 patients using immunohistochemistry to assess the expression of ERCC1. The distribution between treatment arms was equal (36 patients each). Two different
H
scores were calculated and correlated with survival. In ERCC1-positive patients, no significant difference in terms of progression-free survival (PFS) between treatment arms has been detected. ERCC1-negative patients benefited from PGB compared to EB arm (
H
score: HR = 0.377, 95% CI 0.167–0.849,
p
= 0.0151; modified
H
score: HR = 0.484, 95% CI 0.234–1.004,
p
= 0.0468). With respect to the scoring system, in the EB-arm, a significant superior PFS turned out in ERCC1-positive patients when employing the
H
-score (HR = 0.430, 95% CI 0.188–0.981,
p
= 0.0397; median 4.9 vs. 3.9 months), but not with the modified
H
-score. Our findings support the hypothesis that NS-NSCLC displaying a low ERCC1 expression might benefit from cisplatin-based chemotherapy. High expression indicated better PFS in the EB arm supporting the prognostic impact. However, as impact of ERCC1-assessment even might depend on scoring systems differences, the need in standardization of assessment methodology is emphasized.
Abstract
Background
Salivary gland neoplasms represent a heterogeneous group of benign and malignant tumors that comprise 6% of all head and neck cancers. Due to their low incidence, these tumors are ...poorly understood and remain a diagnostic and therapeutic challenge.
Methods
Out of 182 analyzed salivary gland tumors with various histologies, eight were positive for ALK immunohistochemistry. The cut-off was 15% positive cells in either membranous, nuclear or cytoplasmic compartments. The ALK positive tumors were first subjected to FISH analysis. Subsequently, these tumors were analyzed using hybrid capture based next generation sequencing to confirm possible ALK gene fusions or copy number alterations, and to detect additional genomic alterations of clinical relevance.
Results
An in-depth genomic analysis of the samples resulted in the detection of inactivating mutations in BRAF (p.D594N) and TP53 (p.C238S), as well as amplifications of ERBB2 and ALK. Strikingly, a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion was detected in a patient with adenocarcinoma not otherwise specified. This tumor was FISH positive and 100% of cells showed strong membranous staining for ALK. MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion resulted in the retention of the kinase domain of ALK and the coiled-coil domain of MYO18A. Similarly to other ALK fusions, we hypothesize that the coiled-coil domain of MYO18A mediates the dimerization and activation of MYO18A-ALK, thereby resulting in an overexpression of constantly activated ALK.
Conclusion
Using hybrid capture based next generation sequencing, we identified in salivary gland tumors numerous genomic alterations in therapeutically relevant genes and a novel gene fusion (MYO18A-ALK). Patients harboring this fusion may potentially benefit from treatment with ALK inhibitors.
Citation Format: Hanna Majewska, Judith Müller, Sotirios Lakis, Piotr Czapiewski, Adam Gorczyński, Mariola Iliszko, Alena Skalova, Rafal Dziadziuszko, Jacek Jassem, Wojciech Biernat, Roopika Menon, Johannes M. Heuckmann, Lukas C. Heukamp. Genomic profiling of salivary gland tumors identifies novel and targetable alterations. abstract. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3190.
The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness.
Immunohistochemical ...expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB.
There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069).
SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.
Abstract 5101
Enteropathy associated T-cell Lymphoma(EATL) is a distinctive clinicopathological entity but knowledge about potential prognostic factors in this disease is very limited.
...Clinicopathological and immunohistochemical analysis of single center EATL cohort focusing especially on stromal components, activation molecules and potential loss of TCR receptors.
Detailed clinical analysis of a cohort of 21 patients from the southern-west Germany was performed. Additionally broad panel of immunohistochemical staining including MUM1IRF4, Blimp-1, FoxP3, TCR γ, TCRβ, CD11c was done. Univariate statistical analysis of survival was performed.
The study group comprised of 12 males and 9 females, aged 37–86, with the median survival time of 5 months after the initial diagnosis. Following clinical factors turned out to be connected with longer overall survival (OS): age ≤ 60years (p=0, 007), Ann Arbor Stadium I+II (p =0, 048), good general condition (p = 0, 0068), IPI 1–3 (p=0, 004), usage of anthracycline in the chemotherapy regimen (p=0, 0504).
Longer event free survival(EFS) was connected with good general condition (p=0, 023) usage of anthracycline (p=0, 047).
There was 17 Type I cases (81%) and 4 Type II (19%). EATL type, histological variants of neoplastic cells, perivascular and angiocentric growth pattern as well as tissue eosinophilia did not influence survival. There was a strikingly strong infiltration of the neoplastic infiltrate by CD11c+ dendritic cells in 9/21 cases, but it was prognostically irrelevant. MUM1/IRF4 expression was observed in 8/19(42, 1%), Blimp-1 in 5/14 (35, 7%) and FoxP3 in 7/20 (35%), but only FoxP3 positivity was connected with longer EFS. There was a trend toward worse OS (p=0, 18) and EFS (p=0, 12) in Blimp-1 positive cases.
Expression of TCRβ was observed in 4/21(19%), of TCRγ in 3/21(14, 3%) while the majority of cases (14/21), showed loss of expression of both proteins. There was a trend toward longer OS (p=0, 19) and EFS (p=0, 16) in TCR β+ than in TCRγ+ and TCR γ-β- cases.
TCRβ expression was statistically significant more frequent in patients that achieved complete remission (3/7) than in group that did not achieve CR (1/14, p=0, 049).
In EATL several clinical factors can provide relevant prognostic information. Immunohistochemical expression of FoxP3, Blimp-1 and TCRβ seems also to be prognostically usefull. TCRβ is the only marker that can predict response to the chemotherapy in this very aggressive neoplasm.
Finke:Fresenius Biotech GmbH: Honoraria, Research Funding.
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