Welcome to a belated edition of an August 2015 edition of Pulmonary Pathology Reviews, a multi-institutional journal club intended to help you keep pace with the rapidly expanding literature relevant to diagnostic pulmonary pathology. The August teleconference actually occurred on Monday, September 3rd, courtesy of Marie-Christine Aubry at Mayo Clinic Minnesota. What follows is her OVERVIEW and an ARTICLE INDEX that includes links to PubMed Abstracts and full text articles if your institution allows it. Click here for her Cliff Notes-like version of the articles chosen from among those that appeared in print in July 2015. And if you want to hear the teleconference as it went down at 08:15 CDT on Monday, September 3rd click here to download a MP3 audiofile - be patient, it may take awhile to download depending on your internet connection.
The review of the medical literature in July 2015 revealed 21 articles relevant to pulmonary pathology. Four articles were related to the immune system and lung cancer. Although 2 were review articles, these articles seemed to highlight all the current trends on immunotherapy in lung cancer and therefore were chosen for the discussion.
In the first article published in the Journal of Thoracic Oncology, Carbone et al do a systematic review of how the immune system plays a role in both controlling and promoting tumor growth, with emphasis on the checkpoints, CTLA-4 and PD-1. They follow this with a specific review of the current knowledge of the immunity of NSCLC, its correlation with outcome and as a therapeutic target.
The second article by Kerr et al, also in JTO, reviews the current state of the art on the immunohistochemistry of PD-L1, highlighting many of the shortcomings we are or will be facing as the new drugs and their companion test go through various clinical trials.
These 2 articles set us up nicely for the third one by Deng et al, also in JTO. In this study, the authors look at the gene expression of CTLA-4 and PDCD-1 in NSCLC, rather than the commonly used immunohistochemistry, and correlation with various clinical pathologic features, such as histologic subtype, smoking history, stage, survival. Unfortunately, like for most authors not involved directly in the clinical trials, there is no information on how the gene expression correlates with tumor response to checkpoint inhibitors (and perhaps be superior to IHC…or not).
Finally, the 4th article published in the NEJM adds to the growing body of evidence that perhaps we do not need a predictive biomarker. Indeed, in this study summarizing results from a clinical trial comparing standard of care Docetaxel to anti PD-1 Nivolumab in advanced NSCLC, Brahmer et al did not find any correlation between response to treatment with Nivolumab (which appeared superior to Docetaxel) and results of PD-L1 IHC.
There were several excellent and very practical articles published this month that need specific mention. Rami-Porta et al published the recommendations for the new T descriptors for the TNM staging. They do not discuss the recommendations for AIS and MIA which will be published separately. All of us who are members of the PPS received the draft by Travis et al….
Sheffield et al (A. Churg senior author) studies the combination of BAP1 IHC with p16 FISH in distinguishing benign from malignant mesothelial proliferation. Their results show a perfect 100% specificity, if not a high 58% sensitivity in identifying malignant mesothelial proliferation. But most importantly, and which was not mentioned in the article, is BAP1 as a potential therapeutic target with ongoing clinical trials.
Antonescu et al performed a more thorough molecular analysis of IMT. Not all were from the lung (18/62) and the results weren’t focused on the lung IMT. Nonetheless, the results were interesting in suggesting that ALK FISH should be performed instead of IHC with much higher sensitivity. Also, if IMT is at a high stage, a search for rearrangements of not only ALK, but also ROS1 and RET should be performed.
Non–Small-Cell Lung Cancer. Role of the Immune System and Potential for Immunotherapy. Carbone et al. JTO 2015; 10:974 Concise Review
Programmed Death-Ligand 1 Immunohistochemistry in Lung Cancer In what state is this art? Kerr et al. JTO 2015; 10:985 Concise Review
Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non–Small-Cell Lung Cancer. Results from a Large and Pooled Microarray Database. Deng et al. JTO 2015; 10:1020
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer. Brhamer et al. NEJM 2015; 373; 123
Articles for discussion/notation
BAP1 IHC and p16 FISH to separate benign from malignant mesothelial proliferation. AJSP 2015; 39:977
The IASLC Lung Cancer Staging Project. Proposals for the Revisions of the T descriptors in the forthcoming 8th. Rami-Porta et al. JTO 2015; 10:990
Molecular Characterization of Inflammatory Myofibroblastic Tumors With Frequent ALK and ROS1 Gene Fusions and Rare Novel RET Rearrangement. Antonescu et al. AJSP 2015; 39:957
Articles for notation
A bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer. Silvestri et al. NEJM 2015; 373:3
Pulmonary Adenocarcinoma In Situ: Analyses of a Large Series With Reference to Smoking, Driver Mutations, and Receptor Tyrosine Kinase Pathway Activation. Sato et al. AJSP 2015; 39:912
Detailed assessment of microvasculature markers in non-small cell lung cancer reveals potentially relevant characteristics. Pomme et al. Virchows Arch 2015; 467:55
Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer patients. Konig et al. JTO 2015; 10:1049
Routine Clinical Mutation Profiling of NSCLC using NGS. Deeb et al. Arch Pathol Lab Med 2015; 139:913
An Integrated Prognostic Classifier for Stage I Lung Adenocarcinoma Based on mRNA, microRNA and DNA methylation Biomarkers. Robles et al. JTO 2015; 10:1037
Histologic variability in SFT reflects angiogenic and growth factor signaling pathway alterations. Demicco et al. Hum Pathol 2015; 46:1015
French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas. Lantuejoul et al. ERJ 2015; 46:207
Immunohistochemical characterization of the mTOR pathway in stage I NSCLC. Shin et al. Lung Cancer 2015; 89:13
Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium. Iwamoto et al. Human Pathol 2015; 46:957
An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatment of Idiopathic Pulmonary Fibrosis. An Update of the 2011 Clinical Practice Guideline. Raghu et al. Am J Respir Crit Care Med 2015; 192:e3
Diffuse Cystic Lung Disease. Part II. Gupta et al. Am J Respir Crit Care Med 2015; 192:17
ESR/ERS white paper on lung cancer screening. Kauczor et al. Eur Respir J 2015; 46:28
Identification of a Novel ALK G1123S Mutation in a Patient with ALK-rearranged NSCLC Exhibiting Resistance to Ceritinib. Toyokawa et al. JTO 2015; 10:e55