Aggressive tumor microenvironment of solid predominant lung adenocarcinoma subtype harboring with epidermal growth factor receptor mutations
LUNG CANCER
Authors: Saruwatari, Koichi; Ikemura, Shinnosuke; Sekihara, Keigo; Kuwata, Takeshi; Fujii, Satoshi; Umemura, Shigeki; Kirita, Keisuke; Matsumoto, Shingo; Yoh, Kiyotaka; Niho, Seiji; Ohmatsu, Hironobu; Ochiai, Atsushi; Kohrogi, Hirotsugu; Tsuboi, Masahiro; Goto, Koichi; Ishii, Genichiro
Abstract
Introduction: Tumor microenvironment critically affects cancer progression. This study aimed to identify differences in microenvironments of lung adenocarcinomas with epidermal growth factor receptor (EGFR) mutations by histological subtypes. Methods: The study cohort included 214 lung adenocarcinomas harboring EGFR mutations. We analyzed clinicopathological characteristics of lepidic (LPA), papillary (PPA), acinar (APA), and solid-predominant adenocarcinoma (SPA) subtypes, and examined expression levels of EGFR, E-cadherin, ezrin, laminin-5, ALDH1, and PD-L1 in cancer cells, and of CD34, CD204, podoplanin (PDPN), and FoxP3 in stromal cells in 4 subtypes (n=20 each). Results: SPA displayed significantly more frequent lymph node metastasis, lymphovascular invasion, and worse prognosis than the other subtypes. Ezrin expression levels in SPA were also significantly higher than in LPA, PPA, or APA (P < 0.05, all). Laminin-5 and PD-L1 expression levels in SPA were significantly higher than in LPA (P < 0.01 for both) and PPA (P < 0.01 for both) and tended to be higher than in APA (laminin-5: P=0.096, PD-L1: P=0.081). Furthermore, SPA displayed higher levels of PDPN (+) cancer associated fibroblasts (P < 0.01) and CD204 (+) tumor-associated macrophages (P < 0.05) than the other subtypes. Conclusion: Compared with other predominant subtypes with EGFR mutations, the microenvironment of SPA with EGFR mutations is characterized by cancer cells with higher invasive and immune evasion potential and more abundant stromal cells with tumor-promoting functions, which would contribute to the more aggressive behavior of SPA. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Wideband 1.55 mu m Wayeguide Photodiodes Employing Planar Resonant Circuits for E-band (60-90 GHz) Operation
PIERS 2012 MOSCOW: PROGRESS IN ELECTROMAGNETICS RESEARCH SYMPOSIUM
Authors: Rymanov, Vitaly; Lutzmann, Sascha; Palandoeken, Merih; Tekin, Tolga; Stoehr, Andreas
Abstract
The recently regulated 10 GHz bandwidth (71-76 GHz and 81-86 GHz) within the E-band (60-90 GHz) is of particular interest for fixed wireless systems. Since radio-over-fiber (RoF) techniques have opened up the possibility to transmit up to 100 Gb/s in such a wide bandwidth, it is one of the most interesting technologies for ultra-broadband wireless link. In this work, we present E-band waveguide photodiodes (PDs) with high external quantum efficiency, which are required for such ultra-broadband RoF links. In detail, we demonstrate advanced partially p-doped, partially non-intentionally doped (PDPN) absorbing 1.55 mu m waveguide PDs implemented in a mushroom-type layer structure primarily approaching 71-76 GHz operation within the E-band. Furthermore, a passive optical waveguide (POW) is monolithically integrated in the layer structure and is used for efficient optical coupling. As a result, an extremely flat frequency response with a deviation of less than 1 dB in the complete E-band is experimentally achieved. Moreover, an output radio frequency (RF) power level exceeding 0 dBm at a photocurrent in the order of similar to 15 mA is obtained, e.g., at a frequency of 72 GHz. Since no 1 dB compression point is adumbrated, maximum safely working photocurrent levels of 20 mA are expected for cooled operation. For superlative devices, a DC responsivity of up to 0.5 A/W was actually found even without additional anti-reflection (AR) coating. For hybrid integration in a wireless E-band transmitter module, the PDs comprise a grounded coplanar waveguide (GCPW) output circuitry employing linearly tapered feeds. Thus, a matched GCPW circuitry with a 50 Omega output impedance is realized. To ensure a return loss exceeding 20 dB for the 70 GHz band operation, additional LC resonant GCPW circuits were studied and modeled using the method of moments (MoM). Applying the designed GCPW circuitries to the devices, the resulting return loss was optimized about 10-20 dB in the frequency range of 70-90 GHz.