Serviksin LSIL, HSIL ve Skuamöz Hücreli Karsinomlarında Biyopsilerde Ki-67, P16, C-erb B2 ve Siklin D1 Ekspresyonunun Önemi

Year 2018, Volume: 49 Issue: 2, 209 - 213, 07.06.2018

Birgül Tok Şafak Ersöz Gülname Fındık Güvendi

https://doi.org/10.16948/zktipb.377749

Abstract

Amaç:
Serviksin skuamöz hücreli kanseri (SCC), jinekolojik
kanserlerde en sık rastlanan malign tümördür. Skuamoz intraepitelyal lezyonlar
(SIL) preinvazif lezyonlar olarak bilinir. Servikal kanser gelişiminde etkili
lezyonların derecelendirilmesindeki sorunlardan dolayı lezyonların ayrımında
immünohistokimyasal belirteçlerin yararlı olduğu bildirilmiştir. Bu çalışmada,
HSIL ve LSIL olgularında Ki-67, p16, siklin D1 ve c-erb-B2 boyama paterninin
ekspresyonu ve yoğunluğu araştırılmıştır.

Gereç
ve Yöntem: Bu çalışmaya 2003-2011 yılları arasında XXX
Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı'nda teşhis konan 40 SCC, 40
düşük dereceli SIL (LSIL) ve 40 yüksek grade SIL (HSIL) hasta dahil edildi.
Hastaların preparatlarında C-erb-B2, Ki-67, p16 ve siklin D1 ekspresyonları
araştırıldı.

Bulgular:
C-erb-B2, 6 HSIL vakasında (%15), 4 SCC vakasında (%10)
ve 2 LSIL vakasında (%5) pozitif boyanma gösterdi. Gruplar arasında
istatistiksel olarak anlamlı fark yoktu (p> 0.05). Bununla birlikte SCC'li
olgularda c-erb-B2 ile hastalık evresi arasında güçlü bir korelasyon
gözlenmiştir (p<0.05, r = 0.891). Ki-67 ekspresyonu, LSIL vakalarının
ortalama % 20'sinde, HSIL vakalarının ortalama %35'inde ve SCC vakalarının
ortalama %40’ında mevcuttu. Gruplar arasındaki fark, LSIL'den dolayı, istatistiksel
olarak anlamlıydı (p<0.05). Siklin D1 ile nükleer boyanma çoğunlukla LSIL'li
olgularda gözlendi, ancak sitoplazmik boyanma HSIL ve SCC'li olgularda
ağırlıklı olarak gözlendi. Siklin D1 ile, gruplar arasında hiçbir istatistiksel
olarak anlamlı fark gözlenmedi (p>0.05). p16 ekspresyonu HSIL'da 39 (%97.5)
olguda, LSIL’da 12 olguda (% 30) görüldü. Aradaki fark istatistiksel olarak
anlamlıydı (p <0.05).

Sonuç:
Sonuç olarak, c-erb-B2 ve siklin D1 ekspresyonu bu
lezyonların ayrımında yararlı değildir. Bununla birlikte, Ki-67, LSIL'ı HSIL ve
SCC'den ayırmak için kullanılabilir. Ayrıca, p16 ekspresyonunun HSIL ve LSIL'ın
ayrımında yararlı olduğu sonucuna varılmıştır.

Keywords

Ki-67, p16, C-erb-B2, siklin D1, serviks kanseri

The Importance of Ki-67, p16, C-erb-B2, and Cyclin D1 Expressions in LSIL, HSIL, and Cervical Squamous Cell Carcinoma Biopsies

Abstract

Objective:
The squamous cell carcinoma (SCC) of the cervix is the most common malignant
tumor of gynecological cancers. Squamous intraepithelial lesions (SILs) are
known as a preinvasive lesion. Due to problems in the grading of these lesions
that are effective in the development of cervical cancer, immunohistochemical
markers are reported to be useful in the differentiation of lesions. In this
study, the expression and intensity of the staining pattern of Ki-67, p16, cyclin
D1, and c-erb- B2 in HSIL and LSIL cases were investigated.

Material
and Method: 40 patients with SCC, 40 patients with low grade SIL (LSIL),
and 40 patients with high grade SIL (HSIL) who were diagnosed in Department of
Pathology of XXX University Medical Faculty between 2003-2011 years were
included in this study. C-erb-B2, Ki-67, p16, and
cyclin D1 expressions was investigated in the preparations of the
patients.

Results: C-erb-B2
in 4 cases with SCC (10%), in 6 cases with HSIL (15%), and in 2 cases with LSIL
(5%) showed positive staining. There was no statistically significant
difference between the three groups (p>0.05). However, in cases with SCC, a
strong correlation between c-erb-B2 and the disease stage was observed (p<0.05,
r = 0.891). Ki-67 expression was present in average 20% of LSIL cases, average
35% of cases of HSIL, and average 40% of SCC cases. The difference between
groups was statistically significant (p<0.05) and due to LSIL. Nuclear
staining of cyclin D1 was mainly observed in cases with LSIL, however,
cytoplasmic staining was mainly observed in cases with HSIL and SCC. No
statistically significant difference between groups was observed with cyclin D1
(p>0.05). p16 expression was found in 39 (97.5%) cases with HSIL, 12 cases
(30%) with LSIL. The difference was statistically significant (p<0.05).

Conclusion: In
conclusion, c-erb-B2 and cyclin D1 expression is not useful in the differentiation of these
lesions. However, the Ki-67 may be used to separate LSIL from HSIL
and SCC. Also, p16 expression was concluded
to be useful in the differentiation of HSIL and LSIL.

Keywords

Ki-67, p16, C-erb-B2, Cyclin D1, cervical carcinoma

References

• Tavassoli AF, Devilee P: World Health Organization Classification of Tumours Pathology & Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC, 2003: 259-90. 

• Hanhan M, Vardar E, Keleş R, Özbakkaloğlu A, İnal M. Evre I invaziv serviks karsinomları: SSK Ege Doğumevi ve Kadın Hastalıkları Eğitim Hastanesi deneyimi. Ege Tıp Derg 2000;39(1): 51–5. 

• Parkin DM, Bray F, Ferlay J, GLOBOCAN 2002. International Agency for Research on Cancer;55:2.74 

• Stewart BW, Kleihues P. Word Cancer Report. IACR, Lyon, 2003. 

• Kurman R.J, Ellenson L.H, Ronnelt B.M, Blaustein’s Pathology of the Female Genital Tract. Sixth Ed. New York: Springer, 2011: 194–303. 

• Carreras R, Alameda F, Mancebo G, et al A study of Ki-67, c-erbB2 and cyclin D-1 expression in CIN-I, CIN-III and squamous cell carcinoma of the cervix. Histol Histopathol 2007;22:587-92
• Parkin MD, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74–108.
• Seckin S. Servikal intraepitelyal neoplazi ve mikroinvaziv karsinoma. Ank Pat Bult 1993;10(1):20–3.
• Castle PE, Wacholder S, Sherman ME et al, Absolute risc of a subsequent abnormal pap among oncogenic human papillomavirus DNA- positive,cytologically negative women Cancer 2002;95(10):2145-51. 

• Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh ed. Philadelphia: Elsevier Saunders. 2005;1072–9.
• İnsinga RP, Glass AG,Rush BB (2004) Diagnoses and outcomes in cervical cancer screening; a population-based study. Am J Gynecol Pathol 22(1):18-21.
• Benard VB, Lee NC, Piper M et al (2001) Race-specific results of Papanicolaou testing and the rate of cervical neoplasia in the National Brest and Cervical Cancer Early Detection Program,1991-1998 (United States). Cancer Causes Control 12(1):61-8.
• Ersöz Ş, Reis A, Baki N.Trabzon ilinde servikal tarama programı.Türk Jinekoloji ve Obstetrik Derneği Dergisi 2010;7;1:35-9.
• Negri G, Vittadello F, Romano F, Kasal A, Rivasi F, Girlando S, Mian C, Egarter-Vigl E. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 2004;445:616-20.
• Califano D, Losito S, Pisano C, et al Significance of erb-B2 immunoreactivity in cervical cancer. Frontiers in Bioscience 2006;11:2071-6.
• Nakano T, Oka K, Ishikawa A. Morita S. Correlation of cervical carcinoma c-erb B-2 oncogene with cell proliferation parameters in patients treated with radiation therapy for cervical carcinoma. Cancer 1997;79(3):513- 20.
• Mark HF, D. Feldman, S. Das, C.L. Sun, M. Samy, J. Lathrop. HER-2/neu oncogene amplification in cervical cancer studied by fluoresein in situ hybridization. Genet Test 1999;3:237–42.
• Kersemaekers AMF, Fleuren GJ, Kenter GG, Lambert J. C. M. Van den Broek, Uljee SM, Hermans J, Marc J. Van de Vijver. Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clin Cancer Res, 1999;5:577–86.
• Brumm C, Riviere A, Wilckens C, et al. İmmunohistochemical investigation and northern blot analysis of c-erbB2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri. Virchows Arch (A) 1990;417:477-84.