Sains Malaysiana 43(2)(2014):
233–240
Ko-pengekspresan Reseptor Estrogen beta (ERβ) dan Aktin Otot Licin pada Tumor Filodes di Payudara: Suatu Kajian
Tisu Mikroarai
(The Co-expression of
Estrogen Receptor beta (ERβ) and Smooth Muscle Actin in Phyllodes
Tumour of Breast: A Tissue
Microarray Study)
NURHAYATI
H. MUNAWER1,
SITI-AISHAH MD ALI*1,
REENA MD ZIN1
&
ROHAIZAK MUHAMMAD2
1Jabatan Potologi, Pusat Perubatan Universiti Kebangsaan Malaysia
(PPUKM)
56000 Kuala Lumpur, Malaysia
2Jabatan
Surgeri, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
56000
Kuala Lumpur, Malaysia
Received:
6 December 2012/Accepted: 18 May 2013
ABSTRAK
Proliferasi tumor filodes tertumpu
terutama pada bahagian stroma yang dianggap sebagai komponen neoplastik bagi
tumor filodes. Reseptor Estrogen (ER) yang memainkan peranan dalam payudara
neoplastik juga terlibat dalam perkembangan tumor filodes. ERβ adalah satu
jenis klon ER yang dilaporkan hadir pada stroma tumor payudara manakala
pengekspresan aktin otot licin (SMA) di stroma dapat membandingkan gred
histologi tumor filodes. Kami membandingkan pengekspresan ERβ dengan SMA pada
komponen stroma tumor filodes menggunakan teknik tisu mikroarai (TMA). TMA dibentuk
ke atas 77 kes tumor filodes (46 benigna, 17 pinggiran dan 14 malignan)
menggunakan jarum berdiameter 0.6 mm (Alphelys Plaisir, Perancis) dan pewarnaan
imunohistokimia dijalankan menggunakan penanda molekul ERβ dan SMA.
Tumor filodes kerap hadir pada wanita berusia lebih daripada 40 tahun dengan
tumor filodes benigna menunjukkan median umur pesakit paling rendah (p=0.017).
Ekspresi ERβ dalam komponen stroma meningkat dengan gred histologi tumor.
Sementara SMA menunjukkan ekspresi pada 62.8, 41.2 dan 57.1%, masing-masing
bagi tumor filodes benigna, pinggiran dan malignan. Kedua-dua ERβ (p=0.024)
dan SMA lebih cenderung hadir pada wanita ≥40 tahun. Kajian menunjukkan
hubungan signifikan antara ko-pengekspresan ERβ dan SMA (p=0.047) dan
65.5% daripadanya adalah wanita berumur lebih daripada 40 tahun. Ekspresi SMA yang
tinggi pada stroma tumor filodes benigna mungkin menunjukkan potensi
proliferasi tumor ini untuk menjadi malignan. Ekspresi tinggi ERβ dengan
tumor filodes malignan dan hubungannya dengan SMA mencadangkan
ko-pengekspresan kedua-dua penanda molekul ini mungkin berperanan dalam
tumorigenesis stroma tumor filodes.
Kata kunci: ERβ; SMA;
tisu mikroarai; tumor filodes
ABSTRACT
Proliferation of phyllodes tumour is
mainly in the stromal that is considered as the neoplastic component of
phyllodes tumour. Estrogen Receptor (ER) that plays an important role in breast
neoplasm is also involved in progression of phyllodes tumour. ERβ is a
type of ER which was reported to be expressed in the breast stroma while the
expression of smooth muscle actin (SMA) in the stroma may differentiate
histological grade of phyllodes tumour. We compared the expression of ERβ to SMA in
stromal component of phyllodes tumour using tissue microarray (TMA) technique. A TMA was
constructed on 77 cases of phyllodes tumour (46 benign, 17 boderline and 14
malignant) using 0.6 mm punch kit (Alphelys Plaisir, France) and
immunohistochemical staining was done using ERβ and SMA. Phyllodes tumour
seen in women aged more than 40 year-old with benign phyllodes tumour showed
the lowest median of age (p=0.017). ERβ expression in stromal
component increased with histological grade of the tumour. SMA was positive in 62.8,
41.2 and 57.1% of benign, borderline and malignant phyllodes tumour,
respectively. Both ERβ (p=0.024) and SMA were commonly expressed
in women aged ≥40 years. We found a significant co-expression of ERβ and SMA (p=0.047)
and 65.5% of these cases occured in women aged more than 40 years-old. The high
expression of SMA in stroma of benign phyllodes tumour may demonstrate the
potential of proliferation of this tumour to become malignant. High expression
of ERβ of malignant phyllodes tumour and its significant association with SMA suggests
that co-expression of these two markers may play a role in stromal
tumorigenesis of phyllodes tumour.
Keywords: ERβ; phyllodes tumour; SMA;
tissue microarray
REFERENCES
Ang, M.K., Ooi, A.S.,
Thike, A.A., Tan, P., Zhang, Z., Dykema, K., Furge, K., Teh, B.T. & Tan,
P.H. 2011. Molecular classification of breast phyllodes tumors: Validation of
the histologic grading scheme and insights into malignant progression. Breast
Cancer Research Treatment 129: 319- 329.
Bubendorf, L., Nocito,
A., Moch, H. & Sauter, G. 2001. Tissue microarray (TMA) technology: Miniaturized
pathology archives for high-throughput in situ studies. Journal of
Pathology 195: 72-79.
Chen, C.M., Chen, C.J.,
Chang, C.L., Shyu, J.S., Hsieh, H.F. & Harn, H.J. 2000. CD34, CD117, and
actin expression in phyllodes tumor of the breast. Journal of Surgical
Research 94: 84-91.
Chong, J.K. & Woo,
H.K. 1993. Patterns of p53 expression in phyllodes tumors of the breast. Journal
of Korean Medical Science 8(5): 325-328.
Chua, C.L., Thomas, A.
& Ng, B.K. 1989. Cystosarcoma phyllodes: A review of surgical options. Surgery 105: 141- 147.
Cîmpean, A.M., Raica, M.
& Narita, D. 2005. Diagnostic significance of the immunoexpression of CD34
and smooth muscle cell actin in benign and malignant tumors of the breast. Romanian
Journal of Morphology and Embryology 46(2): 123-129.
Clark, S.E., Warwick,
J., Carpenter, R., Bowen, R.L., Duffy, S.W. & Jones, J.L. 2011. Molecular
subtyping of DCIS: Heterogeneity of breast cancer reflected in pre-invasive
disease. British Journal of Cancer 104: 120-127.
Feakins, R.M., Mulcahy,
H.E., Nickols, C.D. & Wells, C.A. 1999. p53 expression in phyllodes tumours
is associated with histological features of malignancy but does not predict
outcome. Histopathology 35: 162-169.
Feakins, R.M., Wells,
C.A., Young, K.A. & Sheaff, M.T. 2000. Platelet-derived growth factor
expression in phyllodes tumors and fibroadenomas of the breast. Human
Pathology 31(10): 1214-1222.
Esposito, N.N., Mohan,
D., Brufsky, A., Lin, Y., Kapali, M. & Dabbs, D.J. 2006. Phyllodes tumor. A
clinicopathologic and immunohistochemical study of 30 cases. Archives
Pathology & Laboratory Medicine 130: 1516–1521.
Glass, A.G., Lacey Jr.,
J.V., Carreon, J.D. & Hoover, R.N. 2007. Breast cancer incidence,
1980-2006: Combined roles of menopausal hormone therapy, screening mammography,
and estrogen receptor status. Journal of the National Cancer Institute 99:
1152-1161.
Gustafsson, J.A. 1999. Estrogen receptor β- a new
dimension in estrogen mechanism of action. Journal of Endocrinology 163:
379-383.
Iau, P.T.,
Lim, T.C., Png, D.J. & Tan, W.T. 1998. Phyllodes tumour: An update of 40
cases. ANNALS Academy of Medicine Singapore 27(2): 200-203.
Jacobs,
T.W., Chen, Y.Y., Guinee, D.G.Jr., Holden, J.A., Cha, I., Bauermeister, D.E.,
Hashimoto, B., Wolverton, D. & Hartzog, G. 2005. Fibroepithelial lesions with
cellular stroma on breast core needle biopsy: Are there predictors of outcome
on surgical excision? American Journal of Clinical Pathology 3: 342-354.
Jara-Lazaro,
A.R. & Tan, P.H. 2009. Molecular pathogenesis of progression and recurrence
in breast phyllodes tumors. American Journal of Translational Research 1(1):
23-34.
Kilarski,
W.W., Jura, N. & Gerwins, P. 2005. An ex vivo model for functional
studies of myofibroblasts. Laboratory Investigation 85(5): 643-654.
Kuijper, A.,
Buerger, H., Simon, R., Schaeter, K.L., Croonen, A., Boecker, W., van der Wall,
E. & van Diest, P.J. 2002. Analysis of the progression of fibroepithelial
tumours of the breast by PCR-based clonality assay. Journal of Pathology 197(5):
575-581.
Liporace,
J., Willcox, K. & Thomas, D.A. 2008. Neurologic considerations in the
postmenopausal women. Dlm Clinical Neurology of the Older Adult. Edisi
ke-2, disunting oleh Siven, J.I. & Malamut, B.L. Philadelphia: Lippincott
Williams & Wilkins. hlm. 54-64.
Munirah,
M.A., Siti-Aishah, M.A., Reena, M.Z., Sharifah, N.A., Rohaizak, M., Norlia, A.,
Rafie, M.K.M., Asimiati, A., Hisham, A., Fuad, I., Shahrun, N.S. & Das, S.
2011. Identification of different subtypes of breast cancer using tissue
microarray. Romanian Journal of Morphology and Embryology 52(2):
669-677.
Nakopoulou,
L., Lazaris, A.C., Panayotopoulou, E.G., Giannopoulou, I., Givalos, N.,
Markaki, S. & Keramopoulos, A. 2004. The favourable prognostic value of
oestrogen receptor β immunohistochemical expression in breast cancer. Journal
of Clinical Pathology 57: 523-528.
Noranizah,
W., Siti-Aishah, M.A., Munirah, M.A., Norazlin, M.H., Rohaizak, M., Naqiyah,
I., Sharifah, N.A. & Das, S. 2010. Immunohistochemical expression of
vascular endothelial growth factor (VEGF) and p53 in breast lesions. Clinica
Terapeutica 161(2): 129-137.
Patrone, C.,
Cassel, T.N., Pettersson, K., Piao, Y.S., Cheng, G., Ciana, P., Maggi, A.,
Warner, M., Gustafsson, J.A. & Nord, M. 2003. Regulation of postnatal lung
development and homeostasis by estrogen receptor beta. Molecular of Cell
Biology 23(23): 8542-8552.
Nurhayati, H.M., Reena, M.Z., Siti-Aishah, M.A., Rohaizak,
M., Jasmi, A.K., Srijit, D. 2012. ER. P53 and MIB-1 are significantly
associated with malignant phyllodee tumor. Biomedical
Journal 35(6): 486-492.
Rousseau,
M.E. 2004. Health care of midlife and aging women. Dlm Varney’s Midwifery.
Edisi ke-4, disunting oleh Varney, H., Kriebs, J.M. & Gegor, C.L. Sudbury:
Jones and Bartlett Publishers.
Sapino, A.,
Bosco, M., Cassoni, P., Castellano, I., Arisio, R., Cserni, G., Dei Tos, A.P.,
Fortunati, N., Catalano, M.G. & Bussolati, G. 2006. Estrogen
receptor-β is expressed in stromal cells of fibroadenoma and phyllodes
tumors of the breast. Modern Pathology 19: 599-606.
Scobie,
G.A., Macpherson, S., Millar, M.R., Groome, N.P., Romana, P.G. & Saunders,
P.T.K. 2002. Human oestrogen receptor: Differential expression of Eralpha and
beta and the identification of Erbeta variants. Steroids 67: 985-992.
Shaaban, A., O’Neill, P.A., Davies, M.P.A., Sibson, R., West, C.R.,
Paul, H. & Christopher, S. 2003. Declining estrogen receptor-[beta]
expression defines malignant progression of human breast neoplasia. The
American Journal of Surgical Pathology 12(27): 1502-1512.
Shantakumar, S., Terry, M.B., Teitelbaum, S.L., Britton, J.A.,
Millikan, R.C., Moorman, P.G., Neugut, A.I. & Gammon, M.D. 2007.
Reproductive factors and breast cancer risk among older women. Breast Cancer
Research and Treatment 102: 365-374.
Sotheran, W., Domjan, J., Jeffrey, M., Wise, M.H. & Perry,
P.M. 2005. Phyllodes tumours of the breast- a retrospective study from
1982-2000 of 50 cases in Portsmouth. Annals of Royal College of Surgeons of
England 87: 339-344.
Speirs, V., Skliris, G.P., Burdall, S.E. & Carder, P.J. 2002.
Distinct expression patterns of ERα and ERβ in normal human mammary
gland. Journal of Clinical Pathology 55: 371-374.
Tan, P.H., Jayabaskar, T., Chuah, K.L., Lee, H.Y., Tan, Y., Hilmy,
M., Hung, H., Selvarajan, S. & Bay, B.H. 2005. Phyllodes tumors of the
breast. The role of pathologic parameters. American Journal of Clinical
Pathology 123: 529-540.
Tan, P.H., Tse, G., Lee, A., Simpson, J.F. & Hanby, A.M.
2012a. Fibroepithelial tumors. Dlm. World Health Organization Classification
of Tumours. Pathology WHO Classification of Tumours of the Breast disunting
oleh Lakhani, S.R., Ellis, I.O., Schnitt, S.J., Tan, P.H. & van de Vijver,
M.J. Lyon: IARC Press.
Tan, P.H., Thike, A.A., Tan, W.J., Myint Thu, M.M., Busmanis, I.,
Li, H., Chay, W.Y., Tan, M.H. & The Phyllodes Tumour Network Singapore.
2012b. Predicting clinical behaviour of breast phyllodes tumours: A nomogram
based on histological criteria and surgical margins. Journal of Clinical
Pathology 65(1): 69-76.
Tsai, W.C., Jin, J.S., Yu, J.C. & Sheu, L.F. 2006. CD10,
Actin, and Vimentin expression in breast phyllodes tumors correlates with tumor
grade of WHO grading. International Journal of Surgical Pathology 14:
127-131.
Tse, M.K., Lee, C.S., Kung, Y.L., Scolyer, F., Law, R.A., Bonita,
K.B., Lau, T.S. & Putti, T.C. 2002. Hormonal receptors expression in
epithelial cells of mammary phyllodes tumors correlates with pathologic grade
of the tumor. A multicenter study of 143 cases. American Journal of Clinical
Pathology 118: 522-526.
Tse, M.K., Chai, B., Lau, K.M., Scolyer, R., Lee, C.S., Karim,
R.Z., Putti, T.C., Law, B.K., Lui, P.C. & Tan, P.H. 2007. Endothelin-1
expression correlates with a typical histological features in mammary phyllodes
tumours. Journal of Clinical Pathology 60(9): 1051-1056.
Wittliff, J.L., Pasic, R. & Bland, K.I. 1998. Steroid and
peptide hormone receptors: Methods, quality control and clinical use. Dlm The
Breast: Comprehensive Management of Benign and Malignant Diseases. Edisi
pertama, disunting oleh Bland, K.I. & Copeland, E.M. Philadephia: Elsevier
Saunder Publisher.
Yonemori, K., Hasegawa, T., Shimizu, C., Shibata, T., Matsumoto,
K., Kauno, T., Ando, M., Katsumata, N. & Fujiwara, Y. 2006. Correlation of
p53 and MIB-1 expression with both the systemic recurrence and survival in
cases of phyllodes tumors of the breast. Pathology, Research & Practice 202:
705-712.
Zainal, A.O. & Nor-Saleha, I.T. 2011. Malaysia Cancer
Statistics- Data and Figure. National Cancer Registry Report. Kuala Lumpur:
Ministry of Health Malaysia.
*Corresponding
author; email: saishah@ppukm.ukm.edu.my
|