Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix

Philip E. Castle; Raheela Ashfaq; Faryal Ansari; Carolyn Y. Muller

doi:10.1016/j.canlet.2005.06.045

Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix

Philip E. Castle, Raheela Ashfaq, Faryal Ansari, Carolyn Y. Muller

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal → HPV infection → Cervical Precancer → Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16 ^INK4a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16^INK4a (P_Trend<0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (P_Trend=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p16^INK4a; HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16^INK4a expression.

Original language	English (US)
Pages (from-to)	245-252
Number of pages	8
Journal	Cancer Letters
Volume	229
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2005.06.045
State	Published - Nov 18 2005
Externally published	Yes

Keywords

Cervical intraepithelial neoplasia
HSP40
HSP60
HSP70
HSP90
Heat shock proteins
Human papillomavirus (HPV)
Immunohistochemistry

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2005.06.045

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@article{24cbae3a5d5142efb2df24bd8158af9f,

title = "Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix",

abstract = "Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal → HPV infection → Cervical Precancer → Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16 INK4a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16INK4a (PTrend<0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (PTrend=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p16INK4a; HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16INK4a expression.",

keywords = "Cervical intraepithelial neoplasia, HSP40, HSP60, HSP70, HSP90, Heat shock proteins, Human papillomavirus (HPV), Immunohistochemistry",

author = "Castle, {Philip E.} and Raheela Ashfaq and Faryal Ansari and Muller, {Carolyn Y.}",

note = "Funding Information: A convenience sample of paraffin-embedded cervical tissues diagnosed as normal ( μm tissue sections were cut from the embedded tissues using a microtome and were used for hematoxylin and eosin (H&E) staining and for immunohistochemistry staining, the latter of which was done in a masked fashion. H&E slides were evaluated for cervical inflammation (no, mild, or severe inflammation), masked to the results of the HSP immunostaining. N =30), cervical intraepithelial neoplasia grade 1 (CIN1)( N =32), and CIN3 were drawn from tissue archives within the Department of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX. We excluded CIN2 from our study because it is a very poorly reproducible histopathologic diagnosis [20] that likely represents a mixture of CIN1 and CIN3; we excluded cancer cases because we were interested in early carcinogenesis and because of the possibility of disease effects. The study was approved by University of Texas Southwestern Medical Center institution review board and was deemed exempt from review by the NIH (Bethesda, MD). Multiple 4 2.2 ",

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T1 - Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix

AU - Castle, Philip E.

AU - Ashfaq, Raheela

AU - Ansari, Faryal

AU - Muller, Carolyn Y.

N1 - Funding Information: A convenience sample of paraffin-embedded cervical tissues diagnosed as normal ( μm tissue sections were cut from the embedded tissues using a microtome and were used for hematoxylin and eosin (H&E) staining and for immunohistochemistry staining, the latter of which was done in a masked fashion. H&E slides were evaluated for cervical inflammation (no, mild, or severe inflammation), masked to the results of the HSP immunostaining. N =30), cervical intraepithelial neoplasia grade 1 (CIN1)( N =32), and CIN3 were drawn from tissue archives within the Department of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX. We excluded CIN2 from our study because it is a very poorly reproducible histopathologic diagnosis [20] that likely represents a mixture of CIN1 and CIN3; we excluded cancer cases because we were interested in early carcinogenesis and because of the possibility of disease effects. The study was approved by University of Texas Southwestern Medical Center institution review board and was deemed exempt from review by the NIH (Bethesda, MD). Multiple 4 2.2

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N2 - Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal → HPV infection → Cervical Precancer → Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16 INK4a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16INK4a (PTrend<0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (PTrend=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p16INK4a; HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16INK4a expression.

AB - Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal → HPV infection → Cervical Precancer → Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N=30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16 INK4a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16INK4a (PTrend<0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (PTrend=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p16INK4a; HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16INK4a expression.

KW - Cervical intraepithelial neoplasia

KW - HSP40

KW - HSP60

KW - HSP70

KW - HSP90

KW - Heat shock proteins

KW - Human papillomavirus (HPV)

KW - Immunohistochemistry

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JO - Cancer Letters

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ER -

Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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