PMID- 32044881
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20210122
IS  - 1533-4058 (Electronic)
IS  - 1533-4058 (Linking)
VI  - 28
IP  - 2
DP  - 2020 Feb
TI  - SERINE-910 Phosphorylated Focal Adhesion Kinase Expression Predicts Better 
      Overall and Disease-free Survival in Melanoma.
PG  - 130-138
LID - 10.1097/PAI.0000000000000744 [doi]
AB  - Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that mediates 
      multiple cellular functions such as survival, invasion, and migration. FAK has 
      been found to be over-expressed in various human cancers, including melanoma. FAK 
      molecule has several tyrosine, serine, and threonine phosphorylation sites which 
      have an important regulatory role. Tyrosine phosphorylation of FAK has been 
      extensively studied, however little is known about the role of serine 
      phosphorylation. We sought to examine the frequency and extent of serine-910 
      phosphorylated FAK (P-FAKSer910) expression in a spectrum of melanocytic 
      proliferations as well as it's correlation with other histopathologic predictors 
      and its effect on patient's survival. Clinicopathologic features and 
      immunohistochemical expression of P-FAKSer910 were evaluated in 147 melanocytic 
      proliferations: 73 primary melanoma (PM), 19 metastatic melanoma (MetM), 2 
      melanoma in situ, and 53 melanocytic nevi (MN). Higher cytoplasmic intensity 
      predicted better overall survival (OS) in PM (chi=5.69; P=0.034) and was associated 
      with 48% decrease in death risk (HR, 0.52; 95% CI, 0.28-0.95; P=0.036). In 
      contrast, increased nuclear intensity was significantly associated with better 
      disease-free survival (DFS) when stratified by tumor stage Log-rank test, trend 
      of survival (chi=5.83, P=0.015) and independently on multivariate analysis when 
      subcategorized into 3-tier categories (HR, 0.43; 95% CI, 0.18-0.98; P=0.045). 
      Also, Clark's level and tumor-infiltrating lymphocytes (TILS) were independent 
      predictors of DFS. Cytoplasmic intensity correlated inversely with American Joint 
      Commission on Cancer stage in primary melanoma cases as well with vascularity in 
      both primary and metastatic melanoma. Nuclear intensity independently correlated 
      negatively with angioinvasion and TILS when subcategorized to 3 tier system. We 
      found American Joint Commission on Cancer tumor stage, Clark's level, depth, 
      ulceration, TILS, mitosis, angioinvasion, and tumor vascularity predictors of 
      both DFS and OS. There was no significant difference in cytoplasmic or nuclear 
      expression among the major categories of melanocytic proliferation. In this pilot 
      immunohistochemistry-based study, we found P-FAKSer910 expression in melanoma by 
      cytoplasmic intensity to correlate with better OS while nuclear intensity 
      correlated with better DFS.
FAU - Najjar, Saleh
AU  - Najjar S
AD  - Department of Pathology, Albany Medical College, MC-81, Albany, NY.
FAU - Homan, Suzanne
AU  - Homan S
FAU - Sheehan, Christine
AU  - Sheehan C
FAU - Carlson, J Andrew
AU  - Carlson JA
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - United States
TA  - Appl Immunohistochem Mol Morphol
JT  - Applied immunohistochemistry & molecular morphology : AIMM
JID - 100888796
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (PTK2 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - Female
MH  - Focal Adhesion Kinase 1/*biosynthesis/genetics
MH  - Follow-Up Studies
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - *Melanoma/enzymology/genetics/mortality/pathology
MH  - Middle Aged
MH  - Phosphorylation
MH  - Serine/genetics/metabolism
MH  - *Skin Neoplasms/enzymology/genetics/mortality/pathology
MH  - Survival Rate
EDAT- 2020/02/12 06:00
MHDA- 2020/11/24 06:00
CRDT- 2020/02/12 06:00
PHST- 2020/02/12 06:00 [entrez]
PHST- 2020/02/12 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
AID - 00129039-202002000-00006 [pii]
AID - 10.1097/PAI.0000000000000744 [doi]
PST - ppublish
SO  - Appl Immunohistochem Mol Morphol. 2020 Feb;28(2):130-138. doi: 
      10.1097/PAI.0000000000000744.