Table 2.

Implications of protein subcellular localization in cancer diagnosis and prognosis

Protein	Relevance to cancer diagnosis and prognosis	Reference
E-cadherin	Nuclear expression, loss of plasma membrane expression, or both was present in 97% of Merkel cell carcinomas, 100% of solid pseudopapillary tumors of the pancreas, and 86% of pituitary adenomas, pancreatic neuroendocrine tumors, clear cell renal cell carcinoma, esophageal squamous carcinoma, colorectal and gastric cancer, or synovial sarcoma.	[69, 176–180]
Epithelial Cell Adhesion Molecule (EPCAM)	Extracellular domain was lost on the plasma membrane but the intracellular domain increased in cytoplasm and nucleus for all epithelial cancers, including thyroid, breast, prostate, head and neck, esophagus, lung, colon, liver, bladder, pancreatic, and ovarian.	[170, 181–183]
Vascular Endothelial Growth Factor Receptor (VEGFR) 2	Positive nuclear staining in invasive lobular breast carcinomas but negative nuclear staining in invasive ductal carcinomas; cytoplasmic localization was more pronounced in patients with melanoma and diffuse large B-cell lymphoma who had poor prognoses.	[99]
Serotonin receptor 1A (5-HTR1A)	Moderate to strong expression, predominantly in the plasma membrane, in all 102 human breast cancer samples; cytoplasmic expression detected in non-malignant cells.	[98]
Epidermal growth factor receptor (EGFR)	Nuclear level was associated with higher local recurrence rate in oropharyngeal squamous cell cancer and with worse disease-free survival in gallbladder carcinoma; cytosolic phosphorylated EGFR was strongly related to increased risk of recurrence and shorter overall survival in penile cancer (36 patients).	[184–187]
Mucin 1 (MUC1)	Expressed on the reversed apical plasma membrane of neoplastic cell clusters in pure invasive micropapillary carcinoma cases but in the whole cytoplasmic membrane or cytoplasm in pseudoinvasive micropapillary carcinomas cases.	[100]
Human Epidermal Growth Factor Receptor 2 (HER2)	Cytoplasmic staining was correlated with neuroendocrine differentiation in breast carcinoma (1053 patients).	[188]
β-Catenin	Cytoplasmic or nuclear expression was strongly associated with poor prognosis and was an independent prognosticator for overall survival in non-small cell lung cancer 309 patients; MTC score (membrane minus cytoplasmic expression) was associated with a worse outcome in invasive ductal breast cancers (292 patients).	[189, 190]
Homeobox Transcription Factor Nanog	Nuclear expression was significantly correlated with nuclear β-catenin expression and poor prognosis in non-small cell lung cancer (309 patients).	[190]
Mammary serine protease inhibitor (MASPIN)	Nuclear expression in 108 tissue samples of laryngeal squamous cell carcinoma was associated with longer disease-free survival.	[191]
Transcriptional Adaptor 3 (ADA3)	Nuclear staining in breast cancer tissues served as a marker of good prognosis; predominant cytoplasmic expression was a marker of poor prognosis in breast cancer (900 cases).	[192]
Cytokine-induced apoptosis inhibitor 1 (CIPIN1)	Nuclear localization was an unfavorable prognostic factor in epithelial ovarian cancer (108 patients).	[193]
NME/NM23 nucleoside diphosphate kinase 1 (NME 1), NME23)	High nuclear expression was associated with a better prognosis in elderly patients with laryngeal carcinoma.	[194]
Cyclin B2	Elevated cytoplasmic level was strongly associated with short-term disease-specific survival of breast cancer patients and with histological tumor type (80 patients).	[195]