Oncotarget Loss of p16 and high Ki67 labeling index is associated with poor outcome

Oncotarget Volume 11, Issue 12 reported that the p16 tumor suppressor is coded by CDKN2A and plays an important role during carcinogenesis and tumor progression in numerous tumor entities.

P16 positivity was found in 30.2% of AC and 13.9% of SCC and CDKN2A deletion in 32.1% of AC and 33.5% of SCC. In AC Ki67 positivity was associated with high tumor stage, presence of lymph node metastasis, high UICC stage and poor grading.

Dr. Nathaniel Melling from the Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany said, "Despite recent advances in the management of the disease, esophageal cancer (EC) is the sixth most lethal malignant disease with nearly half a million novel cases and over 400,000 deaths worldwide."

"Despite recent advances in the management of the disease, esophageal cancer (EC) is the sixth most lethal malignant disease with nearly half a million novel cases and over 400,000 deaths worldwide."

- Dr. Nathaniel Melling, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf

The p16 tumor suppressor has been reported to play a pivotal role in cancer, since it inhibits cyclin-dependent kinases 4 and 6 at the G1 to S-phase transition of the cell cycle and thus prevents phosphorylation of the retinoblastoma protein.

P16 plays an important role during carcinogenesis and tumor progression in numerous tumor entities including cancers of the colon, liver, gallbladder, and skin.

Its expression is associated with unfavorable or favorable tumor phenotype depending on the analyzed tumor entity.

Figure 1: Representative images of p16 immunostaining in (A) p16 cytoplasmatic (red arrow) and nuclear (blue arrow) staining in adenocarcinoma and (B) p16 cytoplasmatic staining in squamous cell carcinoma.

To elucidate the potential role of both p16 expression and CDKN2A deletion as prognostic biomarkers the authors examined our preexisting EC tissue microarray built from tumor samples of more than 690 individual EC patients.

The Melling Research Team concluded in their Oncotarget Research Paper, "the results of our study show that loss of p16 expression - but not CDKN2A deletion - is linked to shortened overall survival in patients with esophageal AC. Furthermore, strong Ki67LI is an independent prognosticator of poor survival in AC. Rare homozygous 9p21 deletions can be considered as catastrophic events leading to complete loss of p16 expression."

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DOI - https://doi.org/10.18632/oncotarget.27507

Full text - https://www.oncotarget.com/article/27507/text/

Correspondence to - Nathaniel Melling - n.melling@uke.de

Keywords - p16, 9p21, esophageal cancer, TMA, prognosis

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