OVER SERÖZ KARSİNOMUNDA VE BORDERLİNE SERÖZ TÜMÖRDE İMMÜNHİSTOKİMYASAL PINCH/LIMS-1 ANTİKOR EKSPRESYONUNUN KLİNİKOPATOLOJİK DEĞERİ
Abstract
Amaç
Özellikle ilginç cys-his zengin proteinin (PINCH/LIMS-
1), tümörlerdeki ve tümörle ilişkili stromadaki kanser
hücrelerinin gelişimini ve yayılımını denetlediği varsayılmaktadır.
Bu çalışmanın amacı, seröz borderline
tümör (SBT) ve seröz karsinomda (SC) tümör ve peritümöral
stromadaki PINCH-1 ekspresyonunu değerlendirmek
ve ekspresyonu ile çeşitli klinik ve patolojik
parametreler arasındaki ilişkileri incelemektir.
Gereç ve Yöntem
Yirmi bir SBT ve 89 SK vakasında PINCH-1 antikorunun
ekspresyonu streptavidin/HRP-biotin ile indirekt
immünoperoksidaz tekniği kullanılarak analiz edilmiştir.
PINCH-1'in tümör ve peritümöral stromadaki
boyanma paterni semikantitatif skorlama yöntemi
kullanılarak değerlendirilmiştir. Çalışmada kullanılan
boyama yöntemi PINCH-1 ekspresyonunun tanımlanmasına
olanak sağlamış ve semikantitatif skorlama
yöntemiyle PINCH-1 boyanmasının yaygınlığı ve
yoğunluğu değerlendirilmiştir. Böylece, PINCH-1 ekspresyonu
ile hasta yaşı, tümör boyutu, FIGO evresi,
intraabdominal yıkama sitolojisi, kapsül invazyonu,
tümör yerleşimi, tümör derecesi ve tanı anındaki kanser
antijen 125 (CA125) seviyeleri gibi çeşitli klinik ve
patolojik faktörler arasındaki korelasyon incelenmiştir.
Bulgular
Çalışmada PINCH-1'in SK vakalarında SBT vakalarına
göre daha yaygın olduğu bulunmuştur. SK’ler SBT
vakalarındakilere göre daha güçlü boyanma göstermiştir
(p<0,001). Çalışmada ayrıca, tümörü çevreleyen
dokudaki PINCH-1 boyanmasının yaygınlığı ve
yoğunluğu ile tümörün tek ya da bilateral overde yer
alması arasında pozitif bir korelasyon bulunmuştur
(dağılım için p = 0,038, yoğunluk için p = 0,024). Bununla
birlikte, PINCH-1 boyanması ile tümör boyutu
arasında negatif bir korelasyon vardı (yaygınlık için
p=0.019, yoğunluk için p=0.007). Ayrıca, PINCH-1 tümör
boyanmasının yoğunluğu, FIGO evresi ve tümör
dereceleri arttıkça istatistiksel anlamlılık sergilemiştir
(sırasıyla p = 0,032 ve p = 0,001).
Sonuç
Bu çalışmanın sonuçları, SK'lerin SBT'lere göre daha
yüksek düzeyde PINCH-1 boyanma yoğunluğu sergilediğini
göstermektedir. Ayrıca, FIGO evresindeki
ve tümör derecesindeki artış, tümör dokusunda artan
PINCH-1 boyanma yoğunluğu ile ilişkilidir. Peritümöral
stromadaki PINCH-1 boyanmasının yayılımı ve yoğunluğu
bilateral tümör vakalarında daha dikkat çekicidir,
ancak tümör boyutuyla ters orantılıdır. PINCH-1
ekspresyonu ile önemli klinikopatolojik faktörler arasında
gözlenen ilişki, bu molekülün seröz over kanseri
gelişiminde rol oynayabileceğini düşündürmektedir.
Çalışmamız PINCH-1'in tümörogenezdeki rolünün
daha iyi anlaşılmasına katkıda bulunabilir ve bu yolağı
hedefleyen yeni terapötik stratejilerin geliştirilmesi için
yol gösterici olabilir.
Keywords
FIGO evresi PINCH/LIMS-1 Seröz borderline tümör Seröz karsinom Seröz over karsinomunda PINCH ekspresyonu
References
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- 2. Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012 Mar;460(3):237–49.
- 3. Desai A, Xu J, Aysola K, Qin Y, Okoli C, Hariprasad R, et al. Epithelial ovarian cancer: An overview. World J Transl Med. 2014 Apr 12;3(1):1–8.
- 4. Prat J. Pathology of cancers of the female genital tract. In: Denny L, editor. International Journal of Gynecology & Obstetrics. 2012. p. S137-50.
- 5. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019 Mar 23;393(10177):1240–53.
- 6. Arora T, Mullangi S, Lekkala MR. Ovarian Cancer [Internet]. StatPearls Publishing; 2023 [cited 2023 Aug 23]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567760/
- 7. McCluggage WG, Singh N, Gilks CB. Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020). Histopathology. 2022 Apr;80(5):762–78.
- 8. Fukuda T, Chen K, Shi X, Wu C. PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J Biol Chem. 2003 Dec 19;278(51):51324–33.
- 9. Lööf J, Rosell J, Bratthäll C, Doré S, Starkhammar H, Zhang H, et al. Impact of PINCH expression on survival in colorectal cancer patients. BMC Cancer. 2011 Mar 22;11:103.
- 10. Yang Y, Wang X, Hawkins CA, Chen K, Vaynberg J, Mao X, et al. Structural basis of focal adhesion localization of LIM-only adaptor PINCH by integrin-linked kinase. J Biol Chem. 2009 Feb 27;284(9):5836–44.
- 11. Wu C. PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. Trends Cell Biol. 2005 Sep;15(9):460–6.
- 12. Wu C. Integrin-linked kinase and PINCH: partners in regulation of cell-extracellular matrix interaction and signal transduction. J Cell Sci. 1999 Dec;112 ( Pt 24):4485–9.
- 13. 1Dougherty GW, Jose C, Gimona M, Cutler ML. The Rsu-1- PINCH1-ILK complex is regulated by Ras activation in tumor cells. Eur J Cell Biol. 2008 Sep;87(8–9):721–34.
- 14. Eke I, Koch U, Hehlgans S, Sandfort V, Stanchi F, Zips D, et al. PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha. J Clin Invest. 2010 Jul;120(7):2516–27.
- 15. Montanez E, Karaköse E, Tischner D, Villunger A, Fässler R. PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm. J Cell Sci. 2012 Nov 1;125(Pt 21):5233–40.
- 16. Sun X-F, Zhang H. Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol Cancer. 2006 Oct 6;5:43.
- 17. Scaife CL, Shea J, Emerson L, Boucher K, Firpo MA, Beckerle MC, et al. Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma. HPB. 2010 Jun;12(5):352–8.
- 18. Davidson B. The diagnostic and molecular characteristics of malignant mesothelioma and ovarian/peritoneal serous carcinoma. Cytopathology. 2011 Feb;22(1):5–21.
- 19. Wang M-W, Gu P, Zhang Z-Y, Zhu Z-L, Li Y-M, Zhao H-X, et al. Expression of PINCH protein in gliomas and its clinicopathological significance. Oncology. 2007;72(5–6):343–6.
- 20. Zhang H-Z, Li X-H, Zhang X, Zhang Z-Y, Meng Y-L, Xu S-W, et al. PINCH protein expression in normal endometrium, atypical endometrial hyperplasia and endometrioid endometrial carcinoma. Chemotherapy. 2010 Aug 11;56(4):291–7.
- 21. Zhu Z-L, Yan B-Y, Zhang Y, Yang Y-H, Wang Z-M, Zhang H-Z, et al. PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Dis Markers. 2012;33(4):171–8.
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- 27. Tingulstad S, Skjeldestad FE, Halvorsen TB, Hagen B. Survival and prognostic factors in patients with ovarian cancer. Obstet Gynecol. 2003 May;101(5 Pt 1):885–91.
- 28. Gilks CB, Ionescu DN, Kalloger SE, Köbel M, Irving J, Clarke B, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol. 2008 Aug;39(8):1239–51.
- 29. Kurman RJ, Ellenson LH, Ronnett BM. Blaustein’s pathology of the female genital tract. 7th ed. Cham, Switzerland: Springer International Publishing; 2019. 1508 p.
- 30. Gao J, Arbman G, Rearden A, Sun X-F. Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. Neoplasia. 2004 Nov;6(6):796–801.
- 31. Wang-Rodriguez J, Dreilinger AD, Alsharabi GM, Rearden A. The signaling adapter protein PINCH is up-regulated in the stroma of common cancers, notably at invasive edges. Cancer. 2002 Sep 15;95(6):1387–95.
- 32. Scaife CL, Shea JE, Dai Q, Firpo MA, Prestwich GD, Mulvihill SJ. Synthetic extracellular matrix enhances tumor growth and metastasis in an orthotopic mouse model of pancreatic adenocarcinoma. J Gastrointest Surg. 2008 Jun;12(6):1074–80.
- 33. Kholodenko BN, Hoek JB, Westerhoff HV. Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends Cell Biol. 2000 May;10(5):173–8.
CLINICOPATHOLOGIC VALUE OF IMMUNOHISTOCHEMICAL PINCH/LIMS-1 ANTIBODY EXPRESSION IN OVARIAN SEROUS CARCINOMA AND BORDERLINE SEROUS TUMOR
Abstract
Objective
Particularly interesting cys-his rich protein (PINCH/
LIMS-1), a protein implicated in cell adhesion, is
assumed to oversee the development and invasion of
cancer cells in tumors and tumor-associated stroma.
This study aimed to assess PINCH-1 expression in
serous borderline tumor (SBT) and serous carcinoma
(SC) in the tumor and peritumoral stroma and
scrutinize any associations between its expression
and various clinical and pathological parameters.
Material and Method
In this study, the expression of the PINCH-1 antibody
was analyzed in 21 cases of SBT and 89 cases of
SC using the indirect immunoperoxidase technique
with streptavidin/HRP-biotin. The staining pattern of
PINCH-1 in the tumor and peritumoral stroma was
evaluated using a semiquantitative scoring method.
The staining procedure used in the study allowed for
the accurate identification of PINCH-1 expression,
and the data obtained through the semiquantitative
scoring method provided a reliable of assessing
the degree and intensity of PINCH-1 staining. Thus,
the correlation between PINCH-1 expression and
various pathologic factors such as patient age, tumor
size, FIGO stage, intra-abdominal washing cytology,
capsule invasion, tumor location in the ovary, tumor
grade, and cancer antigen 125 (CA125) levels at the
time of diagnosis was examined.
Results
The study found that PINCH-1 was more prevalent
in cases of SC than in SBT cases. The tumors in SC
cases had stronger staining than those in SBT cases
(p<0.001). The study also found a positive correlation
between the diffusiveness and intensity of PINCH-1
staining in the tissue surrounding the tumor and
whether the tumor was located on one or both sides of
the ovaries (p = 0.038 for diffusiveness, p = 0.024 for
intensity). However, there was a negative correlation
between PINCH-1 staining and tumor size (p=0.019 for
diffusiveness, p=0.007 for intensity). Furthermore, the
intensity of PINCH-1 tumor staining exhibited statistical
significance in Figo stage and tumor grades as these
increased (p = 0.032 and p = 0.001, respectively).
Conclusion
The results of this study indicate that SCs exhibit a
higher level of PINCH-1 staining intensity than SBTs.
Furthermore, an increase in the FIGO stage and
tumor grade is associated with increased intensity
of PINCH-1 staining in the tumor tissue. Additionally,
the diffusiveness and intensity of PINCH-1 staining
in the peritumoral stroma is more remarkable in
cases of bilateral tumors but is inversely correlated
with tumor size. The observed association between
PINCH-1 expression and important clinicopathologic
factors suggests that this molecule may be involved
in developing serous ovarian cancer. Overall, these
findings may contribute to a better understanding of
the role of PINCH-1 in ovarian tumorigenesis and may
have implications for developing novel therapeutic
strategies targeting this pathway.
Keywords
FIGO stage PINCH/LIMS-1 PINCH expression in serous ovarian carcinoma Serous borderline tumor Serous carcinoma
References
- 1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan;64(1):9–29
- 2. Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012 Mar;460(3):237–49.
- 3. Desai A, Xu J, Aysola K, Qin Y, Okoli C, Hariprasad R, et al. Epithelial ovarian cancer: An overview. World J Transl Med. 2014 Apr 12;3(1):1–8.
- 4. Prat J. Pathology of cancers of the female genital tract. In: Denny L, editor. International Journal of Gynecology & Obstetrics. 2012. p. S137-50.
- 5. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019 Mar 23;393(10177):1240–53.
- 6. Arora T, Mullangi S, Lekkala MR. Ovarian Cancer [Internet]. StatPearls Publishing; 2023 [cited 2023 Aug 23]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567760/
- 7. McCluggage WG, Singh N, Gilks CB. Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020). Histopathology. 2022 Apr;80(5):762–78.
- 8. Fukuda T, Chen K, Shi X, Wu C. PINCH-1 is an obligate partner of integrin-linked kinase (ILK) functioning in cell shape modulation, motility, and survival. J Biol Chem. 2003 Dec 19;278(51):51324–33.
- 9. Lööf J, Rosell J, Bratthäll C, Doré S, Starkhammar H, Zhang H, et al. Impact of PINCH expression on survival in colorectal cancer patients. BMC Cancer. 2011 Mar 22;11:103.
- 10. Yang Y, Wang X, Hawkins CA, Chen K, Vaynberg J, Mao X, et al. Structural basis of focal adhesion localization of LIM-only adaptor PINCH by integrin-linked kinase. J Biol Chem. 2009 Feb 27;284(9):5836–44.
- 11. Wu C. PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. Trends Cell Biol. 2005 Sep;15(9):460–6.
- 12. Wu C. Integrin-linked kinase and PINCH: partners in regulation of cell-extracellular matrix interaction and signal transduction. J Cell Sci. 1999 Dec;112 ( Pt 24):4485–9.
- 13. 1Dougherty GW, Jose C, Gimona M, Cutler ML. The Rsu-1- PINCH1-ILK complex is regulated by Ras activation in tumor cells. Eur J Cell Biol. 2008 Sep;87(8–9):721–34.
- 14. Eke I, Koch U, Hehlgans S, Sandfort V, Stanchi F, Zips D, et al. PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1alpha. J Clin Invest. 2010 Jul;120(7):2516–27.
- 15. Montanez E, Karaköse E, Tischner D, Villunger A, Fässler R. PINCH-1 promotes Bcl-2-dependent survival signalling and inhibits JNK-mediated apoptosis in the primitive endoderm. J Cell Sci. 2012 Nov 1;125(Pt 21):5233–40.
- 16. Sun X-F, Zhang H. Clinicopathological significance of stromal variables: angiogenesis, lymphangiogenesis, inflammatory infiltration, MMP and PINCH in colorectal carcinomas. Mol Cancer. 2006 Oct 6;5:43.
- 17. Scaife CL, Shea J, Emerson L, Boucher K, Firpo MA, Beckerle MC, et al. Prognostic significance of PINCH signalling in human pancreatic ductal adenocarcinoma. HPB. 2010 Jun;12(5):352–8.
- 18. Davidson B. The diagnostic and molecular characteristics of malignant mesothelioma and ovarian/peritoneal serous carcinoma. Cytopathology. 2011 Feb;22(1):5–21.
- 19. Wang M-W, Gu P, Zhang Z-Y, Zhu Z-L, Li Y-M, Zhao H-X, et al. Expression of PINCH protein in gliomas and its clinicopathological significance. Oncology. 2007;72(5–6):343–6.
- 20. Zhang H-Z, Li X-H, Zhang X, Zhang Z-Y, Meng Y-L, Xu S-W, et al. PINCH protein expression in normal endometrium, atypical endometrial hyperplasia and endometrioid endometrial carcinoma. Chemotherapy. 2010 Aug 11;56(4):291–7.
- 21. Zhu Z-L, Yan B-Y, Zhang Y, Yang Y-H, Wang Z-M, Zhang H-Z, et al. PINCH expression and its clinicopathological significance in gastric adenocarcinoma. Dis Markers. 2012;33(4):171–8.
- 22. Foulkes WD, Ragoussis J, Stamp GW, Allan GJ, Trowsdale J. Frequent loss of heterozygosity on chromosome 6 in human ovarian carcinoma. Br J Cancer. 1993 Mar;67(3):551–9.
- 23. Jacobs IJ, Smith SA, Wiseman RW, Futreal PA, Harrington T, Osborne RJ, et al. A deletion unit on chromosome 17q in epithelial ovarian tumors distal to the familial breast/ovarian cancer locus. Cancer Res. 1993 Mar 15;53(6):1218–21.
- 24. Bandera CA, Takahashi H, Behbakht K, Liu PC, LiVolsi VA, Benjamin I, et al. Deletion mapping of two potential chromosome 14 tumor suppressor gene loci in ovarian carcinoma. Cancer Res. 1997 Feb 1;57(3):513–5.
- 25. Brown MR, Chuaqui R, Vocke CD, Berchuck A, Middleton LP, Emmert-Buck MR, et al. Allelic loss on chromosome arm 8p: analysis of sporadic epithelial ovarian tumors. Gynecol Oncol. 1999 Jul;74(1):98–102.
- 26. Lynch HT, Casey MJ, Snyder CL, Bewtra C, Lynch JF, Butts M, et al. Hereditary ovarian carcinoma: heterogeneity, molecular genetics, pathology, and management. Mol Oncol. 2009 Apr;3(2):97–137.
- 27. Tingulstad S, Skjeldestad FE, Halvorsen TB, Hagen B. Survival and prognostic factors in patients with ovarian cancer. Obstet Gynecol. 2003 May;101(5 Pt 1):885–91.
- 28. Gilks CB, Ionescu DN, Kalloger SE, Köbel M, Irving J, Clarke B, et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum Pathol. 2008 Aug;39(8):1239–51.
- 29. Kurman RJ, Ellenson LH, Ronnett BM. Blaustein’s pathology of the female genital tract. 7th ed. Cham, Switzerland: Springer International Publishing; 2019. 1508 p.
- 30. Gao J, Arbman G, Rearden A, Sun X-F. Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer. Neoplasia. 2004 Nov;6(6):796–801.
- 31. Wang-Rodriguez J, Dreilinger AD, Alsharabi GM, Rearden A. The signaling adapter protein PINCH is up-regulated in the stroma of common cancers, notably at invasive edges. Cancer. 2002 Sep 15;95(6):1387–95.
- 32. Scaife CL, Shea JE, Dai Q, Firpo MA, Prestwich GD, Mulvihill SJ. Synthetic extracellular matrix enhances tumor growth and metastasis in an orthotopic mouse model of pancreatic adenocarcinoma. J Gastrointest Surg. 2008 Jun;12(6):1074–80.
- 33. Kholodenko BN, Hoek JB, Westerhoff HV. Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends Cell Biol. 2000 May;10(5):173–8.
Details
| Primary Language | English |
|---|---|
| Subjects | Pathology |
| Journal Section | Araştırma Makaleleri |
| Authors | |
| Publication Date | September 23, 2023 |
| Submission Date | August 24, 2023 |
| Acceptance Date | September 23, 2023 |
| Published in Issue | Year 2023 Volume: 30 Issue: 3 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.