Cancer of unknown primary origin pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: , Roukoz A. Karam, M.D.[2]

Overview

The exact pathogenesis of cancer of unknown primary origin is not fully understood. Several studies noted consistency between metastatic cancer of unknown primary and metastases with known primary origins based on chromosomal abnormalities and overexpression of several genes.


Pathophysiology

Pathogenesis

  • The exact pathogenesis of cancer of unknown primary origin is not fully understood.
  • Cancer of unknown primary, like other cancers, arises from one cell that has managed to escape regulation and produces a tumor at a certain site (the site of origin) and consequently metastasizes to other parts of the body.
  • It is thought that the site of origin of CUP remains unknown due to one or more of the following theories:[1]
    • Remaining small and undetectable clinically
    • Disappearing after metastasizing
    • Elimination by body's defense

Genetics

The factors that keep the primary site of CUP hidden have not yet been identified.

Several studies noted consistency between metastatic cancer of unknown primary and metastases with known primary origins based on chromosomal abnormalities and overexpression of several genes including:

  • Bcl2[2]
    • Bcl-2 expression was seen in 65% of tumors
    • It was found to be overexpressed in 40% of tumors
  • p53[2]
    • Expression of p53 was detected in 70.2% of tumors
    • It was found to be overexpressed in 53% of tumors
  • C-myc[3]
    • 96% of the tumors studied showed positive immunoreactivity for c-myc
  • Ras[3]
    • 92% of the tumors studied showed positive immunoreactivity for Ras
  • C-erbB-2[3]
    • 65% of the tumors studied showed positive immunoreactivity for c-erbB-2

References

  1. 1.0 1.1 Varadhachary GR (2007). "Carcinoma of unknown primary origin". Gastrointest Cancer Res. 1 (6): 229–35. PMC 2631214. PMID 19262901.
  2. 2.0 2.1 Briasoulis E, Tsokos M, Fountzilas G, Bafaloukos D, Kosmidis P, Samantas E; et al. (1998). "Bcl2 and p53 protein expression in metastatic carcinoma of unknown primary origin: biological and clinical implications. A Hellenic Co-operative Oncology Group study". Anticancer Res. 18 (3B): 1907–14. PMID 9677443.
  3. 3.0 3.1 3.2 Pavlidis N, Briassoulis E, Bai M, Fountzilas G, Agnantis N (1995). "Overexpression of C-myc, Ras and C-erbB-2 oncoproteins in carcinoma of unknown primary origin". Anticancer Res. 15 (6B): 2563–7. PMID 8669824.

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