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Laboratory Investigation - Table of Contents alert Volume 97 Issue 2

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Laboratory Investigation


Volume 97, Issue 2 (February 2017)

In this issue
Inside the USCAP Journals
Pathobiology in Focus
Mini Reviews
Research Articles

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Inside the USCAP Journals


Inside the USCAP Journals

2017 97: 116-117; 10.1038/labinvest.2016.144

Full Text

Pathobiology in Focus


Lymphatic invasion and angiotropism in primary cutaneous melanoma

Access of melanoma cells to the cutaneous vasculature either via lymphatic invasion or angiotropism is a proposed mechanism for metastasis. While lymphatic invasion and angiotropism are not currently part of routine melanoma reporting, the detection of these attributes using ancillary immunohistochemical stains may be useful in therapeutic planning for patients with melanoma.

Andrea P Moy, Lyn M Duncan and Stefan Kraft

2017 97: 118-129; advance online publication, December 19, 2016; 10.1038/labinvest.2016.131

Abstract | Full Text

Unexpected UVR and non-UVR mutation burden in some acral and cutaneous melanomas

Whole genome sequencing data generated as part of the Australian Melanoma Genome Project identified 8.6% of acral melanomas with a predominant UVR mutation burden and 2.9% of cutaneous melanomas with a predominant non-UVR mutation burden. This study performs in depth clinicopathological correlation of these interesting cases with contradictory UVR signatures based on the anatomical site of the primary tumor.

Robert V Rawson, Peter A Johansson, Nicholas K Hayward, Nicola Waddell, Ann-Marie Patch, Serigne Lo, John V Pearson, John F Thompson, Graham J Mann, Richard A Scolyer and James S Wilmott

2017 97: 130-145; advance online publication, January 9, 2017; 10.1038/labinvest.2016.143

Abstract | Full Text

The NF1 gene in tumor syndromes and melanoma

NF1 is a tumor suppressor mutated in neurofibromatosis type 1, a RASopathy characterized by neoplasms and pigment aberrations of the skin, eye, and nervous system. NF1 encodes neurofibromin 1, a RAS-GTPase-activating protein. Somatic mutations in NF1 are common in cancer including melanoma. NF1-mutant melanomas are associated with chronic sun-exposure, a high mutation rate, UV signature mutations, and histologic features of desmoplastic melanoma.

Maija Kiuru and Klaus J Busam

2017 97: 146-157; advance online publication, January 9, 2017; 10.1038/labinvest.2016.142

Abstract | Full Text

Mini Reviews


A review of kinase fusions in melanocytic tumors

Translocations resulting in kinase fusions have been recently described in melanocytic neoplasms, particularly those with spitzoid morphology. Seen within approximately half of all spitzoid neoplasms and present within benign, atypical, and malignant lesions, kinase fusions likely represent an early oncogenic event. This review article focuses on kinase fusions described to date in spitzoid neoplasms and how subsequent studies have informed current melanoma research.

Sara C Shalin

2017 97: 158-165; advance online publication, November 28, 2016; 10.1038/labinvest.2016.122

Abstract | Full Text

Immunomodulating property of MAPK inhibitors: from translational knowledge to clinical implementation

This review summarizes the off-target mechanisms of response to BRAF inhibitors and MEK inhibitors and the synergy between targeted therapy and immunotherapy as the biological source to open a window of strategic opportunities for the design of new exciting clinical trials.

Mario Mandalà, Francesco De Logu, Barbara Merelli, Romina Nassini and Daniela Massi

2017 97: 166-175; advance online publication, December 19, 2016; 10.1038/labinvest.2016.132

Abstract | Full Text

Research Articles


Targeting melanoma with front-line therapy does not abrogate Nodal-expressing tumor cells

This study reveals that BRAF-inhibitor (BRAFi) therapy does not target nodal-expressing tumor cells in matched unresectable stage III and IV melanoma patient samples (that preceded eventual death). Accompanying experiments showed the advantage of using combinatorial treatment with BRAFi plus anti-Nodal mAb to suppress tumor growth and metastasis, a significant improvement over monotherapy.

Mary JC Hendrix, Irawati Kandela, Andrew P Mazar, Elisabeth A Seftor, Richard EB Seftor, Naira V Margaryan, Luigi Strizzi, George F Murphy, Georgina V Long and Richard A Scolyer

2017 97: 176-186; advance online publication, October 24, 2016; 10.1038/labinvest.2016.107

Abstract | Full Text

The influence of tumor regression, solar elastosis, and patient age on pathologists’ interpretation of melanocytic skin lesions

The authors surveyed 207 U.S. pathologists to determine whether patient age and tumor characteristics influenced the direction of their diagnosis when interpreting melanocytic skin lesions. The majority (54.6%) reported influence toward a less severe diagnosis by patient age <30, and toward a more severe diagnosis by patient age >70 (58.6%), tumor regression (71.0%), and solar elastosis (57.0%).

Linda Titus, Raymond L Barnhill, Jason P Lott, Michael W Piepkorn, David E Elder, Paul D Frederick, Heidi D Nelson, Patricia A Carney, Stevan R Knezevich, Martin A Weinstock and Joann G Elmore

2017 97: 187-193; advance online publication, November 28, 2016; 10.1038/labinvest.2016.120

Abstract | Full Text

Effects of fatty acid synthase inhibitors on lymphatic vessels: an in vitro and in vivo study in a melanoma model

Fatty acid synthase (FASN) has shown to be overexpressed in melanomas and associated with poor prognosis. FASN inhibitiors decrease the viability, proliferation, migration, filopodia-like extensions of human lymphatic endothelial cells, and the volume of metastases in experimental melanomas. The anti-metastatic properties of these compounds may result from their effects on both lymphatic endothelium and melanoma cells.

Débora C Bastos, Jenny Paupert, Catherine Maillard, Fabiana Seguin, Marco A Carvalho, Michelle Agostini, Ricardo D Coletta, Agnès Noël and Edgard Graner

2017 97: 194-206; advance online publication, December 5, 2016; 10.1038/labinvest.2016.125

Abstract | Full Text

Gene expression profiling of anti-CTLA4-treated metastatic melanoma in patients with treatment-induced autoimmunity

Although ipilimumab therapy in metastatic melanoma improves survival, after initial responses disease progression generally ensues. The authors identify targetable genes that are significantly altered by interaction between a highly activated, ipilimumab -treated immune system and melanoma cells. This study provide insight into how melanomas may evolve to resist checkpoint blockade therapy in spite of systemic evidence of an activated cytotoxic immune response in the form of autoimmunity.

Scott C Bresler, Le Min, Scott J Rodig, Andrew C Walls, Shuyun Xu, Songmei Geng, F Stephen Hodi, George F Murphy and Christine G Lian

2017 97: 207-216; advance online publication, December 5, 2016; 10.1038/labinvest.2016.126

Abstract | Full Text

Vemurafenib and trametinib reduce expression of CTGF and IL-8 in V600EBRAF melanoma cells

The authors explored effects of vemurafenib and trametinib on V600EBRAF-mutated melanoma cell populations. Despite diverse characteristics, all populations responded with reduced expression of IL-8 and CTGF, diminished NF-κB activity and increased percentage of cells with high expression of CD271 and low expression of Ki-67. CTGF inhibition was ERK1/2-dependent but not NF-κB-dependent.

Mariusz L Hartman, Michal Rozanski, Marta Osrodek, Izabela Zalesna and Malgorzata Czyz

2017 97: 217-227; advance online publication, January 9, 2017; 10.1038/labinvest.2016.140

Abstract | Full Text



Selective deletion of adipocytes, but not preadipocytes, by TNF-α through C/EBP- and PPARγ-mediated suppression of NF-κB

Minori Tamai, Tsuyoshi Shimada, Nobuhiko Hiramatsu, Kunihiro Hayakawa, Maro Okamura, Yasuhiro Tagawa, Shuhei Takahashi, Shotaro Nakajima, Jian Yao and Masanori Kitamura

2017 97: 228; 10.1038/labinvest.2016.124

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