TY - JOUR
T1 - Characterization of molecular markers indicative of cervical cancer progression
AU - Arnouk, Hilal
AU - Merkley, Mark A.
AU - Podolsky, Robert H.
AU - Stöppler, Hubert
AU - Santos, Carlos
AU - Álvarez, Manuel
AU - Mariategui, Julio
AU - Ferris, Daron
AU - Lee, Jeffrey R.
AU - Dynan, William S.
PY - 2009
Y1 - 2009
N2 - Cervical cancer originates with human papillomavirus (HPV) infection and progresses via histologically defined premalignant stages. Here we compare normal cervical epithelium and patient-matched high-grade squamous intraepithelial lesions (HSIL) with cervical carcinoma tissue from the same patient population (n = 10 per group). Specimens were analyzed by combined laser capture microdissection and 2-D DIGE. Significant expression changes were seen with 53 spots resulting in identification of 23 unique proteins at the molecular level. These include eight that uniquely distinguish normal epithelium and HSIL and four that uniquely distinguish HSIL and carcinoma. In addition, one protein, cornulin, distinguishes all three states. Other identified proteins included differentiation markers, oncogene DJ-1, serpins, stress and interferon-responsive proteins, detoxifying enzymes, and serum transporters. A literature review, performed for all identified proteins, allowed most changes to be assigned to one of three causes: direct or indirect HPV oncoprotein interactions, growth selection during latency, or interactions in the lesion microenvironment. Selected findings were confirmed by immunohistochemistry using either frozen sections from the same cohort or formalin fixed paraffin embedded samples from a tissue microarray. Novel markers described here have potential applications for increasing the predictive value of current screening methods.
AB - Cervical cancer originates with human papillomavirus (HPV) infection and progresses via histologically defined premalignant stages. Here we compare normal cervical epithelium and patient-matched high-grade squamous intraepithelial lesions (HSIL) with cervical carcinoma tissue from the same patient population (n = 10 per group). Specimens were analyzed by combined laser capture microdissection and 2-D DIGE. Significant expression changes were seen with 53 spots resulting in identification of 23 unique proteins at the molecular level. These include eight that uniquely distinguish normal epithelium and HSIL and four that uniquely distinguish HSIL and carcinoma. In addition, one protein, cornulin, distinguishes all three states. Other identified proteins included differentiation markers, oncogene DJ-1, serpins, stress and interferon-responsive proteins, detoxifying enzymes, and serum transporters. A literature review, performed for all identified proteins, allowed most changes to be assigned to one of three causes: direct or indirect HPV oncoprotein interactions, growth selection during latency, or interactions in the lesion microenvironment. Selected findings were confirmed by immunohistochemistry using either frozen sections from the same cohort or formalin fixed paraffin embedded samples from a tissue microarray. Novel markers described here have potential applications for increasing the predictive value of current screening methods.
KW - 2-D DIGE
KW - Cervical cancer
KW - High-grade squamous intraepithelial lesion (HSIL)
KW - Human papillomavirus
KW - Laser capture microdissection
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U2 - 10.1002/prca.200800068
DO - 10.1002/prca.200800068
M3 - Article
AN - SCOPUS:67649429402
SN - 1862-8346
VL - 3
SP - 516
EP - 527
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 5
ER -