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BAB 5. KESIMPULAN DAN SARAN

5.2. Saran…

1. Pemeriksaan imunohistokimia MMP-9 dianjurkan untuk dilakukan secara rutin pada pemeriksaan biopsi lesi prakanker serviks karena dapat memberikan informasi progresivitas penyakit sebelum lesi prakanker menjadi lesi invasif.

2. Diperlukan penelitian lanjutan untuk melihat ketepatan diagnosis histopatologi dan imunohistokimia dalam hubungannya dengan ukuran specimen biopsi lesi prakanker serviks dan kanker serviks invasif.

DAFTAR PUSTAKA

1. Edianto D. Kanker serviks. Dalam : Aziz F, Andrijono, Saifuddin AB, editor. Buku acuan nasional : Onkologi Ginekologi. Cetakan pertama. Jakarta: Yayasan Bina Pustaka Sarwono Prawirohardjo. 2006 ; 442-54.

2. Rosai J. Rosai and Ackerman’ s : Surgical Pathology. 9th edition. Vol 2. Philadelphia : Mosby. 2004; 1523-51.

3. Putra AD, Moegni EM. Lesi prakanker serviks. Dalam : Aziz F, Andrijono, Saifuddin AB, editor. Buku acuan nasional : Onkologi Ginekologi. Cetakan pertama. Jakarta : Yayasan Bina Pustaka Sarwono Prawirohardjo. 2006; 399-412.

4. Hacker NF. Cervical cancer. In : Berek JS, Hacker NF, editors. Practical gynecologic oncology. 4th edition. Philadelphia : Lippincott Williams & Wilkins. 2005; 337-86.

5. Holschneider CH. Epidemiology, clinical features, and diagnosis of invasive cervical cancer. Available at : http://www.UpToDate.com. 2005.

6. Bertelsen BI. Uterine cervical neoplasia : aspects of biology and pathology. The Gade institute section for pathology Department of Pathology Institute Haukeland University Hospital, University of Bergen. 2006.

7. Saslow D, Runowicz CD, Solomon D, Moscick AB, Smith RA, et al. American cancer society guideline for the early detection of cervical neoplasia and cancer . CA Cancer J Clin. 2002; 52:342-62.

8. Crum CP, Lester SC, Cotran RS. The female genital system and breast. In : Kumar V, Cotran RS, Robbins S, editors. Robbins basic

pathology. International 7 th edition. Philadelphia : Saunders. 2003; 684-9.

9. Crum CP, Rose PG. Cervical squamous neoplasia. In : Crum CP, Lee KR editor. Diagnostic gynecologic and obstetric pathology. Philadelphia: Elsevier Saunders, Inc. 2006; 267–344.

10. Campion MJ. Preinvasive disease. In : Berek JS, Hacker NF, editors. Practical gynecologic oncology. 4th edition. Philadelphia : Lippincott Williams & Wilkins. 2005; 265-310.

11. Solomon D, Nayar R. The Bethesda system for reporting cervical cytology. 2nd edition. New York : Springer-Verlag. 2004; v-viii.

12. Rundhaug JE. Matrix metalloproteinases, angiogenesis, and cancer. Clin. Cancer Res. 2003; 9:551–4.

13. Gaiotto MAM, Focchi J, Ribalta JLC, Stavale JN, et al. Comparative study of MMP-2 (Matrix Metalloproteinase 2) immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma. Am J Obstet Gynecol. 2004 ; 190:1278-82.

14. Eiffel PJ, Berek JS, Markman MA. Cancers of the cervix, vagina and vulva. In : DeVita VT, Hellman S, et al editors. Cancer : principles and practice of oncology. Book II. 7th ed. Philadelphia : Lippincott Williams and Wilkins. 2005 ; 1295-317.

15. Wells M, Ostor AG, Crum CP, Franschesci S, et al. Epithelial tumors of the uterine cervix. In : Tavasolli FA, Devilee P, editors. Pathology and genetics of tumours of the breast and female genital organs. World Health Organization classification of tumours. Lyon : WHO IARC Press. 2003 ; 259-71.

16. Crum CP, Nucci MR, Lee KR. The Cervix. In : Mills SE, Carter D et al, editors. Sternberg’s diagnostic surgical pathology. Vol 2. 4th ed. Philadelphia : Lippincott Williams & Wilkins. 2004; 2378-415.

17. Robboy SJ, Duggan MA, Kurman RJ. The female reproductive system. In : Rubin E, Farber JL editors. Pathology. 2nd ed. Philadelphia : JB Lippincott. 1994 ; 922-31.

18. Kraus FT. Female genitalia. In : Kissane J editor. Anderson’s pathology. Vol 2. International 9th ed. St. Louis : CV Mosby Company. 1990; 1643-52.

19. Terry DM. Premalignant disease of the cervix, vagina and vulva. In : Frederickson HL, Wilkins-Haug L, editors. OBGYN secrets. 2nd edition. 117-9.

20. Chandrasoma P,Taylor CR. Concise pathology. 3rd ed. Singapore : McGraw-Hill. 2001; 790-4.

21. Palefsky JM, Cranston RD. Virology of human papillomavirus infections and the link to cancer. Available at : http://www.UpToDate.com. 2005.

22. Feldman S, Goodman A. Approach to screening for cervical cancer. Available at: http://www.UpToDate.com. 2005.

23. Richart RM. Cervical cancer precursors and their management. In : Rock JA, Thompson JD, editors. Te Linde’s operative gynecology. 8th ed. Philadelphia : Lippincott Raven. 1997 ; 1385-409.

24. Leveno KJ, Cunningham FG, Gunt NF, Alexander JM, et al. Williams manual of obstetrics. 21st edition. New York : McGraw Hill, 2003 ; 612-3.

25. Novak ER, Woodruff JD. Novak’s Gynecologic and obstetric pathology. Philadelphia : WB Saunders. 1962; 88- 119.

26. Shingleton HM, Thompson JD. Cancer of cervix. In : Rock JA, Thompson JD, editors. Te Linde’s operative gynecology. 8th ed. Philadelphia : Lippincott Raven. 1997 ; 1413-36.

27. Barclay L. Watchful waiting may be appropriate for some women with HPV. Medscape Medical News – CME. J Natl Cancer Inst. 2008; 100:513-7.

28. Frederickson H. Carcinoma of the uterine cervix. In : Frederickson HL, Wilkins-Haug L, editors. OBGYN secrets. 2nd edition. 121-4.

29. Netter’s obstetrics, gynecology and women’s health. International edition. Canada : Icon Learning Systems LLC. 2002 ; 78-90.

30. Datta M, Randall L, Holmes N, Karunaharan N. Rapid obstetrics and gynecology. Massachusetts : Blackwell Publishing. 2003; 16.

31. Dutta DC. Textbook of obstetrics. 5th edition. Calcutta : New Central Book Agency (P) Ltd. 325-7.

32. Carr PL, Ricciotti HA, Freund KM, Kahan S. In a page : OB/GYN and women’s health. Philadelphia : Lippincott Williams and Wilkins. 2007 ; 53.

33. Jones L, Ghaneh P, Humphreys M, Neoptolemos JP. The matrix metalloproteinases and their inhibitors in the treatment of pancreatic cancer. Annals New York Academy Of Sciences. 288-307.

34. Zugibe FT. Diagnostic histochemistry. St. Louis : CV.Mosby company. 1970; 103.

35. Roomi MW, Ivanov V, Niedzwiecki A, Rath A. Suppression of MMP expression and invasion of human cervical cancer cell lines Hela and DoTc2 4510 by nutrients. Presented at : 44th Annual meeting of the society of toxicology. New Orleans. March 6-10, 2005.

36. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9–expressing macrophages and angiogenesis to impair cervical carcinogenesis. J. Clin. Invest. 2004 ; 114(5):623-633 .

37. Decock J, Paridaens R, Ye S. Genetic polymorphisms of matrix metalloproteinases in lung, breast and colorectal cancer. Clin Genet . 2008; 73:197–221.

38. Rundhaug JE. Matrix metalloproteinases and angiogenesis. J. Cell. Mol. Med. 2005; 9(2):267-85.

39. Goodsell DS. The molecular perspective : Matrix metalloproteinase 2. The oncologist. 1999 ; 4(6):509-11.

40. Duncan ME, Richardson JP, Murray GI, Melvin WT, Fothergill JE. Human matrix metalloproteinase-9: activation by limited trypsin treatment and generation of monoclonal antibodies specific for the activated form. Eur. J. Biochem. 1998; 258:37-43.

41. O-charoenrat P, Rhys-Evans PH, Eccles SA. Expression of matrix metalloproteinases and their inhibitors correlates with invasion and

metastasis in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2001; 127:813-20.

42. Lee MH, Murphy G. Matrix metalloproteinases at a glance. Journal of Cell Science. 2004 ; 117:4015-6.

43. Kelloff GJ, Lippman SC, Dannenberg AJ, Sigman CC, Pearce HL, et al. Progress in chemoprevention drug development : the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer : A plan to move forward. Clin Cancer Res. 2006; 12(12):3661-97.

44. Bennett JH, Morgan MJ, Whawell SA, Atkin P, Roblin P, et al. Metalloproteinase expression in normal and malignant oral keratinocytes : stimulation of MMP-2 and -9 by scatter factor. Eur J Oral Sci. 2000; 108:281-91.

45. Chen Y, Miller C, Mosher R, Zhao X, Deeds J, et al. Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Research. 2003 ; 63:1927–35.

46. Blain E, Curtis C. The impact of proteinases on matrix biology. Int. J. Exp. Path. 2003; 84:A1–A21.

47. Elkins PA, Yen SH, Smith WW, Janson CA, D'Alessio KJ, et al. Structure of the C-terminally truncated human ProMMP9, a gelatin-binding matrix metalloproteinase. Acta Cryst. 2002; D58:1182-92. 48. Notoatmodjo S. Metodologi penelitian kesehatan. Edisi revisi. Jakarta:

Rineka Cipta. 2002.

49. Berek JS. Simplification of the new Bethesda 2001 classification system. Am J Obstet Gynecol. 2003; 188(3):S2-S5.

LAMPIRAN 1 DATA BAKU PENELITIAN

TAMPILAN IHK MMP-9 PADA LESI NEOPLASTIK INTRAEPITEL DAN KARSINOMA INVASIF SERVIKS

No .

No. Slide Nam a

Umur Pap Smear Specimen Histopato

(H & E

1. 258.pa.08 CA 35 thn Pap II LEEP LGSIL 2. 387.pa.08 J 29 thn Pap I Biopsi LGSIL

3. 51.pa.08 U 40 thn Pap II (HPV) Biopsi LGSIL +radang 4. 06.pa.09 TSC 47 thn Pap II Biopsi LGSIL +radang 5. 92.pa.09 S 35 thn Pap II Biopsi LGSIL

6. 11.pa.09 LFN 45 thn Pap II Biopsi LGSIL 7. 388.pa.08 TTS 53 thn Pap II Biopsi LGSIL 8. 428.pa.08 TS 48 thn Pap III (Displasia ringan) Biopsi LGSIL 9. 254.pa.08 SG 35 thn Pap II Biopsi LGSIL 10. 07.pa.09 N 24 thn Pap II Biopsi LGSIL

11. 225.pa.08 NTN 38 thn Pap III (Displasia ringan) Biopsi LGSIL + radang 12. 323.pa.08 SE 47 thn Pap II Biopsi LGSIL

13. 19.pa.09 N 34 thn Pap III (Displasia ringan) Biopsi LGSIL

14. 66.pa.09 F 44 thn Pap IV (Displasia sedang) Biopsi LGSIL + radang 15. 03.pa.09 R 27 thn Pap I Biopsi LGSIL

16. 62.pa.09 Z 47 thn Pap IV (Displasia sedang-berat)

Biopsi LGSIL + HGSIL se 17. 263.pa.08 GS 42 thn Pap II LEEP HGSIL

18. 283.pa.08 SG 35 thn Pap III (Displasia ringan) LEEP HGSIL 19. 61.pa.08 UI 40 thn Pap II (HPV) LEEP HGSIL

No .

No. Slide Nam a

Umur Pap Smear Specimen Histopato

(H & E

20. 57.pa.08 NY 29 thn Pap II Biopsi HGSIL

21. 418.pa.08 NP 29 thn Pap II LEEP HGSIL + radang 22. 338.pa.08 A 30 thn Pap III (Displasia ringan) LEEP HGSIL

24. 04.pa.09 Wi 28 thn Pap IV (Displasia sedang) Biopsi HGSIL 25. 255.pa.08 S 43 thn Pap II Biopsi HGSIL 26. 386.pa.08 P 42 thn Pap IV (Displasia

sedang-berat)

Biopsi HGSIL 27. 68.pa.09 IA 28 thn Pap II LEEP HGSIL

28. 30.pa.09 S 44 thn Pap III (Displasia ringan) Biopsi HGSIL + radang 29. 70.pa.09 KL 35 thn LEEP HGSIL

30. 43.pa.09 LD 30 thn Pap III (Displasia ringan) Biopsi HGSIL

31. 61.pa.09 K 35 thn Pap II LEEP HGSIL + radang 32. N.

924.06

H 45 thn Pap II Biopsi HGSIL (Ca Insitu) 33. N.1320.0

8

L 52 thn Pap II Biopsi HGSIL (Ca Insitu) 34. 557.O.08 Sa 52 thn Pap III (Displasia ringan) TAH Ca invasif (Non ker

KGB)

35. 320.O.08 Su 48 thn Pap II TAH Ca invasif (Non ker 36. 805.B.08 H 57 thn Pap III (Displasia ringan) Biopsi Ca invasif (Non ker 37. 340.O.08 RY 34 thn Pap II TAH Ca invasif (Non ker 38. 1903.O.0

8

Si 54 thn Pap III (Displasia ringan) TAH Ca invasif (Non ker KGB)

39. 532.B.08 S 54 thn Pap III (Displasia ringan) Biopsi Ca invasif (Non ker 40. 1741.B.0

8

RH 56 thn Pap II (HPV) Biopsi Ca invasif (Non ker 41. 1538.B.0

8

Ru 46 thn Pap IV (Displasia sedang) Biopsi Ca invasif (Non ker angioinvasi)

No .

No. Slide Nam a

Umur Pap Smear Specimen Histopato

(H & E

42. 1804.B.0 8

EP 28 thn Pap II Biopsi Ca invasif (Non ker 43. 5511.O.0

8

DL 34 thn Pap III (Displasia ringan) TAH Ca invasif (Non Ker +angioinvasi) 44. 1965.O.0

8

SN 45 thn Pap III (Displasia ringan) TAH Ca invasif (Non ker KGB)

45. 3445.O.0 8

N 32 thn Pap II TAH Ca invasif (Non ker KGB)

46. 03.B.08 I 51 thn Pap II Biopsi Ca invasif (Non Ker +angioinv)

47. 168.B.08 S 54 thn Pap III (Displasia ringan) Biopsi Ca invasif (Non ker 48. 1197.O.0

8

M 32 thn Pap II TAH Ca invasif (Non ker 49. 019.B.08 EP 46 thn Pap II Biopsi Ca invasif (Non ker 50. 316.B.08 R 46 thn Pap II Biopsi Ca invasif (Non ker

KETERANGAN

Pap smear : hasil sitopatologi Pap’smear yang terdahulu sebelum dilakukan biopsi.

Pap I : Tidak ada kelainan

Pap II : Inflamatori smear (bisa karena HPV, non spesifik, jamur)

Pap III : Displasia ringan

Pap IV : Displasia sedang- berat

Pap V : Karsinoma

Specimen : cara memperoleh jaringan

• LEEP : Loop Electrosurgical Excision Procedure (biopsi dengan alat elektrokauter)

• Biopsi : Punch biopsy, biopsi eksisi

TAH : Total Abdominal Histerektomi

Histopatologi prosedur konvensional dengan Hematoksilin & Eosin, didapat diagnosa :

• LGSIL : Low Grade Squamous Intraepithelial Lesion

(displasia ringan)

• HGSIL : High Grade Squamous Intraepithelial Lesion

(displasia

sedang – berat termasuk Ca insitu)

Ca invasif : Non keratinizing Squamous Cell Carcinoma (sudah menembus membran basal)

Bisa saja sudah ada angioinvasi (menembus pembuluh darah) dan metastase kelenjar getah bening

IHK MMP-9 : Imunohistokimia dengan antibodi Matrix Metalloproteinase 9, jaringan terpulas positif di epitel dan atau stroma.

Skor kuantitas : F = Fokal (setempat) D = Diffuse (merata) Skor intensitas : 0 = negatif 1 = lemah

2 = sedang 3 = kuat

LAMPIRAN 2

FOTO-FOTO MIKROSKOPIS IMUNOHISTOKIMIA MMP-9

A B

Gambar 1. Jaringan karsinoma invasif dengan tampilan IHK MMP-9 intensitas kuat dan diffuse pada stroma A.Pembesaran 40x; B. Pembesaran 100x

Gambar 2. Biopsi Ca serviks invasif dengan skor intensitas +3 kuat yang terpulas fokal pada epitel permukaan (x200).

Gambar 3. Sediaan Ca invasif den tampilan IHK MMP-9 intensitas dan diffuse pada epitel ser (x100).

Gambar 4. Jaringan dengan tampilan IHK MMP-9 intensitas kuat dan diffuse pada epitel karsinoma invasif (x100).

Gambar 5. Jaringan HGSIL denga tampilan IHK MMP-9 intensitas ku namun fokal pada epitel dan nega pada stroma (x100).

Gambar 6. Jaringan HGSIL dengan tampilan IHK MMP-9 intensitas sedang dan diffuse pada epitel dan pada stroma (x100).

Gambar 7. Sediaan Ca insitu (HGSIL dengan tampilan IHK MMP-9 memiliki intensitas sedang dan diffuse pada epitel dan stroma (x100).

Gambar 9. Ekspresi positif kuat da diffuse pada jaringan hepar sebaga kontrol positif IHK (x200).

Gambar 8. Jaringan LGSIL dengan tampilan IHK MMP-9 intensitas sedang dan fokal pada epitel dan lemah pada stroma (x100).

DAFTAR RIWAYAT HIDUP

Nama : Dr. Jessy Chrestella

NIP : 132 325 719

Tempat/ Tgl Lahir : Medan, 13 Januari 1982 Jenis Kelamin : Wanita

Status : Menikah

Agama : Kristen

Alamat : JL. Dr. Mansur No. 77

Medan – 20131, INDONESIA Telepon : 061- 8211272 / HP. 08126023988

Email : jes_ch@msn.com / jes_ch_99@yahoo.com

Nama suami : Dr. Wahyudi Gani, SpOG Nama anak : Samuel Joe Anderson Gani

Grace Abigail Gani

RIWAYAT PENDIDIKAN :

1. SD St. Yoseph II Medan – tahun 1987 - 1993 2. SMP St. Thomas 1 Medan – tahun 1993 - 1996 3. SMA St. Thomas 1 Medan – tahun 1996 - 1999

4. Fakultas Kedokteran Universitas Sumatera Utara – tahun 1999 - 2004.

5. Pendidikan Dokter Spesialis Patologi Anatomi, Fakultas Kedokteran Universitas Sumatera Utara, Januari 2006 - sekarang.

PARTISIPASI DALAM KEGIATAN ILMIAH :

1. Peserta pelatihan Basic Life Support Education Program, Medan, 10-11 November 2001.

2. Panitia 2nd Asean Conference on Medical Sciences, Medan, 18-20 Agustus 2002.

3. Peserta Simposium Early Detection of Ovarian Cancer, Medan, 4-5 Oktober 2003.

4. Peserta Pelatihan Advanced Cardiac Life support (ACLS), USU, MEDAN, 27-29 MEI 2005.

5. Peserta Kursus Neuropatologi, Medan, 18 Maret 2006.

6. Peserta Pertemuan Ilmiah IDI Cabang Medan, Medan, 13 Januari 2007.

7. Peserta Seminar Waspada Kanker pada Anak - IDAI dan USU, Medan, 24-25 Maret 2006.

8. Peserta Kursus Patologi Limforetikuler dan Sumsum Tulang, Jakarta, 24-25 Maret 2007.

9. Peserta 24th World Congress of Pathology and Laboratory Medicine, Kuala Lumpur, 20-24 Agustus 2007.

10. Peserta Simposium Upaya Deteksi Dini Karsinoma Nasofaring di Sumatera Utara, Medan, 29 April 2008.

11. Peserta Kursus Patologi Ginekologi, Jakarta, 3-4 Mei 2008.

12. Panitia Seminar awam Deteksi Dini dan Pencegahan Kanker pada Wanita, Medan, 14 Juni 2008.

13. Peserta Konferensi Kerja ke-11 dan Pertemuan Ilmiah Tahunan (PIT) Perhimpunan Dokter Spesialis Patologi Anatomi (IAPI), Manado, 15-18 Juli 2008.

14. Peserta Kursus Patologi Tiroid dan Payudara, Jakarta, 13-14 Desember 2008.

15. Peserta Seminar dan Workshop Dermatopatologi, Medan, 25-26 Januari 2009.

17. Peserta Kursus Patologi Gastrointestinal, Jakarta, 25-26 April 2009. 18. Panitia Kongres Nasional Perhimpunan Dokter Spesialis Patologi

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