title: Punctate LC3B expression is a common feature of solid tumors and associated with proliferation, metastasis, and poor outcome.
abstract: OBJECTIVE
  Measurement of autophagy in cancer and correlation with histopathologic grading or clinical outcomes has been limited. Accordingly, we investigated LC3B as an autophagosome marker by analyzing nearly 1,400 tumors from 20 types of cancer, focusing on correlations with clinical outcomes in melanoma and breast cancer.
  
  
  METHODS
  Staining protocols were developed for automated quantitative analysis (AQUA) using antibodies versus LC3 isoform B (LC3B) and Ki-67. Clinically annotated breast and melanoma tissue microarrays (TMA) and a multitumor array were used. An AQUA program was developed to quantitate LC3B distribution in punctate and diffuse compartments of the cell.
  
  
  RESULTS
  LC3B staining was moderate to high in the large majority of tumors. The percentage of area occupied by punctate LC3B was elevated by 3- to 5-fold at high LC3B intensities. In breast cancer and melanoma TMAs, LC3B and Ki-67 showed strong correlations (P < 0.0001), and in multitumor TMAs, mitotic figures were most often seen in tumors with the highest LC3B expression (P < 0.002). In breast cancer, LC3B expression was elevated in node-positive versus node-negative primaries and associated with increased nuclear grade and shortened survival. In a melanoma TMA with no survival data, LC3B levels were highest in nodal, visceral, and cutaneous metastases.
  
  
  CONCLUSIONS
  The results reveal a common expression of LC3B in malignancy and support emerging evidence that autophagy plays a significant role in cancer progression. High LC3B was associated proliferation, invasion and metastasis, high nuclear grade, and worse outcome. Thus, autophagy presents a key target of therapeutic vulnerability in solid tumors.
authors.affiliation: Departments of Dermatology and Pathology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Rossitza
authors.initials: R
authors.lastname: Lazova
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: Vincent
authors.initials: V
authors.lastname: Klump
authors.forename: Summar F
authors.initials: SF
authors.lastname: Siddiqui
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Amaravadi
authors.forename: John M
authors.initials: JM
authors.lastname: Pawelek
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism / Q000556:secondary*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000378:metabolism / Q000556:secondary*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D021381:Protein Transport; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins
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