Tumor marker for colorectal cancer

Review Article

ÊÒú‹§ªÕéÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ

Tumor marker for colorectal cancer

âÊÀ³ ¨ØµÔÍÁÃàÅÔÈ ÀѷþÔÁ¾ ÊÃþÇÕÃǧȏ

Sopon Jutiamornlert Patrapim Sunpaweravong

˹‹ÇÂÁÐàÃç§ÇÔ·ÂÒ ÀÒ¤ÇÔªÒÍÒÂØÃÈÒʵÏ ¤³Ðá¾·ÂÈÒʵÏ

ÁËÒÇÔ·ÂÒÅÑÂʧ¢ÅÒ¹¤ÃÔ¹·Ã Í.ËÒ´ãËÞ‹ ¨.ʧ¢ÅÒ 90110 Unit of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand E-mail: sopon92001@hotmail.com

Songkla Med J 2010;28(2):97-102

º·¤Ñ´Â‹Í:

ÁÕ¡ÒÃ¹Ó Carcinoembryonic antigen (CEA) áÅÐ Cancer antigen 19-9 (CA19-9) ÁÒ㪌໚¹ ÊÒú‹§ªÕéÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡÁÒ¡·ÕèÊØ´

à¾×èÍ㪌»ÃÐàÁÔ¹¼Å¡ÒÃÃÑ¡ÉÒ µÔ´µÒÁ¡ÒáÅѺ໚¹«éÓ

¢Í§ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ ໚¹»ÃÐ⪹

㹡ÒÃÇҧἹ¡ÒÃÃÑ¡ÉÒ·ÕèàËÁÒÐÊÁ

¤ÓÊÓ¤ÑÞ: µÑǺ‹§ªÕé, ·ÇÒÃ˹ѡ, ÁÐàÃç§, ÅÓäÊŒãËÞ‹

ÃѺµŒ¹©ºÑºÇѹ·Õè 30 ¸Ñ¹ÇÒ¤Á 2551 ÃѺŧµÕ¾ÔÁ¾Çѹ·Õè 23 ÁÕ¹Ò¤Á 2552

Abstract:

Carcinoembryonic antigen (CEA) and Cancer antigen 19-9 (CA19-9) are the two

most common tumor markers for colorectal cancer that are currently utilized clinically for investi- gation. Simultaneous use of the two markers is useful in evaluating the therapeutic effect and monitoring the recurrence of advanced colorectal cancer.

Key words: cancer, colorectal, marker, tumor

º·¹Ó

»˜¨¨ØºÑ¹»ÃÐà·Èä·ÂÁÕ¼ÙŒ»†ÇÂÁÐàÃç§à¾ÔèÁÁÒ¡¢Öé¹ â´Â੾ÒÐÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ ¡ÒÃ㪌ÊÒú‹§ªÕé âäÁÐàÃç§ (tumor marker) ª‹ÇÂãËŒ¡ÒÃÇҧἹ㹡Òà ÃÑ¡ÉÒä´Œ¼Å´ÕÂÔ觢Öé¹ ¨Ö§ÁÕ¡ÒÃ㪌ÊÒú‹§ªÕéâäÁÐàÃ秡ѹÍ‹ҧ

á¾Ã‹ËÅÒ â´Â੾ÒÐ carcinoembryonic antigen ËÃ×Í CEA ã¹¼ÙŒ»†ÇÂÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ ¡Ò÷ÃÒº

¶Ö§¢ŒÍº‹§ªÕé¢Í§¡ÒÃÊ‹§µÃǨÊÒôѧ¡Å‹ÒÇ µÅÍ´¨¹¡Òà µÔ´µÒÁáÅлÃÐàÁÔ¹¼Å¨Ðª‹ÇÂãËŒà¡Ô´»ÃÐÊÔ·¸Ô¼Å µ‹Í¡ÒÃÃÑ¡ÉÒÁÒ¡ÂÔ觢Öé¹

µÑǺ‹§ªÕé·Ò§ªÕÇà¤ÁբͧâäÁÐàÃç§ (tumor marers) ÊÒú‹§ªÕéâäÁÐàÃç§à»š¹ÊÒÃâ»ÃµÕ¹·ÕèäÁ‹¾ºã¹ÀÒÇл¡µÔ ËÃ×ÍÍҨ໚¹ÊÒ÷ÕèÁÕã¹ÀÒÇл¡µÔᵋÁÕã¹»ÃÔÁÒ³·ÕèäÁ‹ÊÙ§

àÁ×è͵ÃǨ¾ºÊÒÃàËÅ‹Ò¹ÕéËÃ×;ºÇ‹ÒÊÒÃàËÅ‹Ò¹ÕéÁÕ»ÃÔÁÒ³ÊÙ§

ÁÒ¡¨¹¼Ô´»¡µÔ¨Ðª‹Çº‹§ªÕéËÃ×ͺ‹§¶Ö§¤ÇÒÁÊÑÁ¾Ñ¹¸¡Ñºâä

ÁÐàÃç§ ¨Ö§ä´ŒÁÕ¡ÒùÓÁÒ㪌·Ò§¤ÅÔ¹Ô¡à¾×èͪ‹ÇÂÇÔ¹Ô¨©ÑÂâä

ÁÐàÃç§ »˜¨¨ØºÑ¹ÂѧäÁ‹ÁÕÊÒú‹§ªÕéµÑÇã´·Õè¨Ð¨Óà¾ÒÐÁÒ¡·ÕèÊØ´

áÅÐÊÒÁÒö㪌㹡ÒõÃǨ¾ºÁÐàÃç§ã¹ÃÐÂÐááàÃÔèÁä´Œ ¡àÇŒ¹ã¹âäÁÐàÃ秺ҧª¹Ô´«Öè§ÁÕÊÒú‹§ªÕéâäÁÐàÃç§à©¾ÒÐ

¡ÑºÍÇÑÂÇйÑé¹æ ઋ¹ ÁÐàÃ秵‹ÍÁÅÙ¡ËÁÒ¡ ໚¹µŒ¹ ¼Å

¡ÒõÃǨ¢Í§ÊÒú‹§ªÕéâäÁÐàÃç§ã¹àÅ×Í´¨ÐµŒÍ§´Ù¤‹Ò͌ҧÍÔ§

(cut off reference) ¢Í§ª¹Ô´¹éÓÂÒ·Õè㪌㹡Ò÷´Êͺ µÑǺ‹§ªÕé·Õè¨Óà¾Òе‹ÍâäÁÐàÃç§ÅÓäÊŒãËÞ‹áÅÐ

·ÇÒÃ˹ѡ (specific markers of colorectal cancer)

The American Society of Clinical Oncology (ASCO) »‚ ¾.È. 2549 ä´ŒÁÕ¡ÒÃà¼Âá¾Ã‹¤Ù‹Á×Í¡ÒÃ㪌 ÊÒú‹§ªÕéÊÓËÃѺâäÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡäÇŒ¹ ´Ñ§¹Õé (µÒÃÒ§·Õè 1)

- Carcinoembryonic antigen (CEA) - Cancer antigen 19-9 (CA 19-9)

- DNA ploidy or Flow cytometric proli- ferationanalysis

- Protein 53 (P53) - Ras

- Thymidylate synthase (TS), Dihy- dropyrimidine dehydrogenase (DPD) and Thymidine phosphorylase (TP) - Microsatellite instability (MSI)/hMSH2

or hMLH1

- 18q-/deleted colon cancer (DCC) Carcinoembryonic antigen

Gold áÅÐ Freedman² ໚¹¼ÙŒ·Õè·Óãˌǧ¡ÒÃᾷ

µÒÃÒ§·Õè 1 áÊ´§ÊÒú‹§ªÕéã¹âäÁÐàÃç§ÅÓäÊŒãËÞ‹²²

ÊÒú‹§ªÕé ¡ÒõÃǨ ¡ÒÃÃкØÃÐÂÐâä/ ¡ÒõÃǨà¾×è͵ԴµÒÁ ¡ÒÃÃÑ¡ÉÒàÁ×è͵ÃǨ¾º à¾×èͤѴ¡Ãͧ ¡ÒÃÇҧἹ¡ÒÃÃÑ¡ÉÒ ¡ÒÃá¾Ã‹¡ÃШÒÂËÅѧ¼‹ÒµÑ´

CEA äÁ‹ 㪌à¾×èÍ¡ÒÃʹѺʹع㹠·Ø¡ 3 à´×͹µ‹Íà¹×èͧÍ‹ҧ¹ŒÍ ·Ø¡ 1-3 à´×͹ÃÐËÇ‹Ò§ãËŒ¡Òà ¡ÒÃÇҧἹ¡ÒÃÃÑ¡ÉÒËÃ×Í 3 »‚ËÅѧ䴌ÃѺ¡ÒÃÇÔ¹Ô¨©ÑÂÇ‹Ò ÃÑ¡ÉÒã¹¼ÙŒ»†ÇÂÁÐàÃç§

ºÍ¡ÃÐÂТͧâä äÁ‹ãªŒ ໚¹ÁÐàÃç§ ã¹¼ÙŒ»†ÇÂÁÐàÃç§ÃÐÂÐ á¾Ã‹¡ÃШÒÂ

à¾×è͵ѴÊÔ¹ã¨ã¹¡ÒÃãËŒÂÒ 2 ËÃ×Í 3

à¤ÁպӺѴàÊÃÔÁËÅѧ¼‹ÒµÑ´

CA 19-9 äÁ‹ äÁ‹ 㪌䴌㹼ٌ»†ÇºҧÃÒ·ÕèÁÕ¡Òà ·Ø¡ 1-3 à´×͹ÃÐËÇ‹Ò§ãËŒ¡ÒÃ

µÃǨáŌǾº¤‹ÒÊÙ§¡‹Í¹¡Òà ÃÑ¡ÉÒã¹¼ÙŒ»†ÇÂÁÐàÃç§

ÃÑ¡ÉÒ á¾Ã‹¡ÃШÒ (੾ÒÐã¹¼ÙŒ»†ÇÂ

·ÕèÁÕ¡ÒõÃǨáŌǾº¤‹ÒÊÙ§

¡‹Í¹¡ÒÃÃÑ¡ÉÒ) DNA ploidy äÁ‹àËÁÒÐÊÁ äÁ‹ äÁ‹àËÁÒÐÊÁ äÁ‹àËÁÒÐÊÁ

P53 äÁ‹ äÁ‹ äÁ‹ äÁ‹

Ras äÁ‹ äÁ‹ äÁ‹ äÁ‹

TS, TP, DPD äÁ‹ äÁ‹ äÁ‹ äÁ‹

MSI äÁ‹àËÁÒÐÊÁ äÁ‹ äÁ‹àËÁÒÐÊÁ äÁ‹

18q-LOH/DCC äÁ‹àËÁÒÐÊÁ äÁ‹ äÁ‹àËÁÒÐÊÁ äÁ‹

ÃÙŒ¨Ñ¡¡Ñº CEA «Öè§à»š¹ÊÒú‹§ªÕéâäÁÐàÃç§ÅÓäÊŒãËÞ‹·Õè㪌 º‹Í·ÕèÊØ´ CEA ÁÕÍÂÙ‹ã¹ÅÓäÊŒãËÞ‹¢Í§·Òá㹤ÃÃÀ

(fetal colon) áÅÐÁÐàÃç§ÅÓäÊŒãËÞ‹ª¹Ô´ÍдÔ⹤ÒÏ«Ôâ¹ÁÒ (colon adenocarcinoma) ᵋ¾ºã¹ÅÓäÊŒãËÞ‹¢Í§¼ÙŒãËÞ‹

·ÕèÁÕÊØ¢ÀÒ¾´Õã¹»ÃÔÁÒ³¹ŒÍ ¨Ö§àÃÕÂ¡Ç‹Ò Carcinoem- bryonic antigen^3,4

CEA ໚¹ä¡Åâ¤â»ÃµÕ¹ (glycoprotein) ÁÕ¢¹Ò´

180-200 ¡ÔâÅ´Òŵѹ⁴ ÁÕº·ºÒ·ã¹àÃ×èͧ¢Í§¡ÒÃà¡ÒеԴ

(adhesion) áÅÐÂѺÂÑ駡ÒÃà¡Ô´¡Ãкǹ¡ÒÃÊÅÒÂà«Åŏ

(apoptosis) ÁÕ¤‹Ò¤ÃÖ觪ÕÇÔµ 3 Çѹ ÃдѺ»¡µÔ¨ÐµèÓ¡Ç‹Ò 5 äÁâ¤Ã¡ÃÑÁµ‹ÍÅÔµÃ⁵ 㹤¹·ÕèäÁ‹ÊÙººØËÃÕèÁÕ¤‹ÒµèÓ¡Ç‹Ò 2.5

¹Ò⹡ÃÑÁµ‹ÍÁÔÅÅÔÅԵà áÅÐ㹤¹·ÕèÊÙººØËÃÕè¨ÐµèÓ¡Ç‹Ò 5.0

¹Ò⹡ÃÑÁµ‹ÍÁÔÅÅÔÅÔµÃ

ËÅѡࡳ±¡ÒõÃǨ CEA áÅСÒûÃÐàÁÔ¹¼Å 1. ¡ÒÃËÒÃÐÂТͧâ䡋͹¡Òü‹ÒµÑ´ (preopera- tive for staging) à¹×èͧ¨Ò¡ CEA äÁ‹ä´ŒÁÕ¤ÇÒÁ¨Óà¾ÒÐ ÁÒ¡¹Ñ¡ ʋǹãËÞ‹áŌǨзӡÒõÃǨàÁ×èÍ·ÃÒºÍÂÙ‹áÅŒÇ Ç‹Ò¼ÙŒ»†ÇÂ໚¹ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ â´ÂÍÒÈÑÂ

¼Å·Ò§¾ÂÒ¸ÔÇÔ·ÂÒ㹡ÒÃÃкØÃÍÂâä «Ö觡Ò÷Õè CEA ÁÕ¤‹ÒÊÙ§¨Ðº‹§ºÍ¡Ç‹ÒÃÍÂâäÁÑ¡ÍÂÙ‹ã¡ÅŒËÅÍ´àÅ×Í´

㪌à¾×èͪ‹ÇÂ㹡ÒÃÇҧἹ¡ÒÃÃÑ¡ÉÒ àª‹¹ ¡ÒÃãËŒÂÒ à¤ÁպӺѴàÊÃÔÁ (adjuvant chemotherapy) 㹡óշÕè CEA ÊÙ§ à¾×èͪ‹ÇÂÅ´¢¹Ò´¡ŒÍ¹à¹×éͧ͡ŧ Ê‹§¼ÅãËŒ

¡Òü‹ÒµÑ´ÁÕ»ÃÐÊÔ·¸ÔÀÒ¾ áÅÐÁÕÀÒÇÐá·Ã¡«ŒÍ¹¹ŒÍ 2. ËÅѧ¡Òü‹ÒµÑ´ (postoperative) 㪌㹡Òà µÔ´µÒÁ¼ÅÇ‹Ò¼‹ÒµÑ´¡ŒÍ¹à¹×éͧ͡䴌ËÁ´ËÃ×ÍäÁ‹ â´Â à»ÃÕºà·ÕºÃдѺ CEA ¡‹Í¹áÅÐËÅѧ¡Òü‹ÒµÑ´ ¶ŒÒ¤‹Ò ŴŧáÊ´§Ç‹Ò¡Òü‹ÒµÑ´ä´Œ¼Å´Õ «Öè§ÃдѺ CEA ¨ÐŴŧ

ÀÒÂã¹ 6-8 ÊÑ»´Òˏ⁶

3. à¾×èÍ´Ù¡ÒõͺʹͧËÅѧ¡ÒÃÃÑ¡ÉÒ´ŒÇÂÂÒ ÃдѺ CEA ¨ÐŴŧàÁ×èÍ¡ÒÃÃÑ¡ÉÒä´Œ¼Å â´Â¤ÇõԴµÒÁÃдѺ CEA ·Ø¡ 3 à´×͹ µÔ´µ‹Í¡Ñ¹Í‹ҧ¹ŒÍ 3 »‚

4. ¼ÙŒ»†Ç·Õèä´ŒÃѺÂÒ Oxaliplatin ¨ÐÁÕÃдѺ CEA ŴŧªŒÒ ÃдѺ CEA ¨ÐŴŧËÅѧ¡ÒÃÃÑ¡ÉÒ 4-6 ÊÑ»´Òˏ

5. äÁ‹á¹Ð¹ÓãËŒµÃǨ¤Ñ´¡Ãͧ¼ÙŒ»†ÇÂÁÐàÃç§ÅÓäÊŒãËÞ‹

áÅзÇÒÃ˹ѡ´ŒÇ CEA

6. ¡ÒõÃǨ CEA ÁÕ¤ÇÒÁäÇ áÅФÇÒÁ¨Óà¾ÒÐ µ‹ÍÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡÌÍÂÅÐ 45 áÅÐ 88 µÒÁÅӴѺ⁶

7. ¶ŒÒ¼ÙŒ»†ÇÂÁÕÃдѺ CEA ¡‹Í¹¡Òü‹ÒµÑ´ÁÒ¡¡Ç‹Ò 5 Á¡.µ‹ÍÁÅ. º‹§ªÕé¶Ö§¡ÒþÂҡóâääÁ‹´Õ à¹×èͧ¨Ò¡

ÁÑ¡¾ºÇ‹Òà¹×éͧ͡ÍÂÙ‹ã¡ÅŒËÅÍ´àÅ×Í´ áÅÐÁÑ¡¨Ð¡ÃШÒ 仵ÒÁ·Õ赋ҧæ áÅŒÇ àª‹¹ µÑº »Í´ ¡Ãд١ ËÃ×ÍáÊ´§Ç‹Ò

¡ŒÍ¹à¹×éͧ͡ÁÕ¢¹Ò´ãËÞ‹ ¤Ç÷Õè¨ÐãËŒÂÒà¤ÁպӺѴàÊÃÔÁ⁷ 8. ¶ŒÒ¼ÙŒ»†ÇÂÁÕÃдѺ CEA ¹ŒÍÂ¡Ç‹Ò 30 Á¡.µ‹ÍÁÅ. ¨Ð ÁÕ¤‹ÒÁѸ°ҹ¢Í§ÍѵÃÒ¡ÒÃÃÍ´ªÕÇÔµ»ÃÐÁÒ³ 34.8 à´×͹⁶ 9. ¶ŒÒ¼ÙŒ»†ÇÂÁÕÃдѺ CEA ÁÒ¡¡Ç‹Ò 30 Á¡.µ‹ÍÁÅ.

¤‹ÒÁѸ°ҹ¢Í§ÍѵÃÒ¡ÒÃÃÍ´ªÕÇÔµ»ÃÐÁÒ³ 22 à´×͹⁶ 10. ÃдѺ CEA Ê٧䴌㹼ٌ»†Ç·ÕèäÁ‹ÁÕâäÁÐàÃç§

ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ ᵋÁÕâä¡ÃÐà¾ÒÐÍÒËÒÃÍÑ¡àʺ (gastritis) á¼Å㹡ÃÐà¾ÒÐÍÒËÒà (peptic ulcer disease: PUD) âäµÔè§à¹×éÍã¹ÅÓäÊŒãËÞ‹ÍÑ¡àʺ (diver- ticulitis) âäµÑº (liver disease) âä»Í´ÍØ´¡Ñé¹àÃ×éÍÃѧ

(chronic obstructive pulmonary disease:

COPD) âäàºÒËÇÒ¹ ËÃ×ÍÁÕ¡ÒÃÍÑ¡àʺ·Õèã´·Õè˹Öè§

·Ñé§áººà©Õº¾ÅѹáÅÐàÃ×éÍÃѧ

Cancer antigen 19-9 (CA 19-9)

໚¹ä¡Åâ¤â»ÃµÕ¹ª¹Ô´ÁÔÇ«Ô¹ (mucin) «Ö觨Ѻ¡Ñº monoclonal antibody ª¹Ô´ 1116-NS 19-9 (mAb 1116 NS 19-9)⁸ ¢¹Ò´ 210 ¡ÔâÅ´Òŵѹ ໚¹ÊÒà à¡ÒеԴÀÒÂã¹à«Åŏ (intracellular adhesion) ¾ºã¹ ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ䴌ÌÍÂÅÐ 30 ¤‹Ò»¡µÔ 0-37 ÂÙ¹Ôµµ‹ÍÅԵà ¤‹Ò¤ÃÖ觪ÕÇÔµ 1 Çѹ⁵ ÃŒÍÂÅÐ 5-10 ¢Í§

¤¹·ÑèÇ仨ÐäÁ‹ÁÕà͹ä«Á·Õè㪌㹡Ãкǹ¡ÒÃÊÌҧ CA 19-9 ´Ñ§¹Ñ鹶ŒÒ¨Ð㪌໚¹ÊÒú‹§ªÕéã¹ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅÐ

·ÇÒÃ˹ѡ¡ç¨ÐÁÕâÍ¡ÒʼԴ¾ÅÒ´ÃŒÍÂÅÐ 5-10 ઋ¹¡Ñ¹^9,10 ¡ÒÃ㪌 CA 19-9 㹡ÒõÃǨµÔ´µÒÁ¼ÙŒ»†ÇÂÁÐàÃç§

ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ¤ÇÃÁÕ¡ÒûÃÐàÁÔ¹·Ø¡ 1-3 à´×͹

ÃдѺ¢Í§ CA 19-9 ·Õèà¾ÔèÁ¢Ö鹨ÐàËÁ×͹¡Ñº CEA ¹Ñ蹤×Í º‹§ªÕéÇ‹ÒÁÕ¡ÒÃÅØ¡ÅÒÁ¢Í§âä äÁ‹ãªŒ¡ÒõÃǨÃдѺ CA 19-9 㹡ÒäѴ¡ÃͧÃÐÂТͧâä¹

DNA ploidy

¡ÒõÃǨ DNA ploidy ËÃ×ͨӹǹªØ´¢Í§â¤ÃâÁâ«Á ã¹ÊÒ¾ѹ¸Ø¡ÃÃÁ àÃÕ¡ÍÕ¡Í‹ҧNjҡÒÃÇÔà¤ÃÒÐˏ¨Ó¹Ç¹ªØ´

â¤ÃâÁâ«Á¢Í§ÊÒ¾ѹ¸Ø¡ÃÃÁ´ŒÇÂà·¤¹Ô¤â¿Åä«- âµàÁ·ÃÔ¤ (fl ow cytometric proliferation analysis) (à¾×èÍ´ÙÍѵÃÒʋǹ¢Í§à«ÅŏÁÐàÃç§ÃÐÂÐÊѧà¤ÃÒÐˏ´ÕàÍç¹àÍ) ໚¹¡ÒÃÇÑ´»ÃÔÁÒ³ÊÒþѹ¸Ø¡ÃÃÁ (DNA content) ·ÕèÍÂÙ‹

ã¹à«ÅŏÁÐàÃç§ ãªŒã¹¡ÒþÂҡó¢Í§ÁÐàÃç§ÅÓäÊŒãËÞ‹

áÅзÇÒÃ˹ѡÃÐÂÐàÃÔèÁáá ¶ŒÒÃдѺ DNA ploidy ÊÙ§

¼ÙŒ»†Ç¨ÐÁÕÃÐÂÐàÇÅÒ㹡ÒÃÃÍ´ªÕÇÔµËÅѧ¼‹ÒµÑ´Å´Å§

Í‹ҧÁÕ¹ÑÂÊÓ¤ÑÞ (p < 0.05)^1,11 P53 (protein 53)

P53 ËÃ×Í TP53 (tumor protein 53) ໚¹â»ÃµÕ¹

·ÕèÁÕÁÇÅâÁàÅ¡ØÅ 53 ¡ÔâÅ´Òŵѹ à¡Ô´¨Ò¡¡ÒäѴÊÓà¹Ò

¢Í§ÂÕ¹ TP53 ·Ó˹ŒÒ·Õè㹡ÒäǺ¤ØÁǧ¨Ã¢Í§à«Åŏ

¤ÅŒÒ¡Ѻ໚¹Ë¹‹ÇÂÃÑ¡ÉÒ¤ÇÒÁ»ÅÍ´ÀÑ¢ͧ¨Õâ¹Á (genome) â´Â໚¹µÑÇÂѺÂÑ駡ÒÃà¡Ô´à¹×éͧ͡ËÃ×ÍÁÐàÃç§

(tumor suppressor protein)¹²

ÁÕ¡ÒÃÃÒ§ҹ P53 ¤ÃÑé§ááâ´Â Baker áÅФ³Ð¹³ ã¹»‚ ¾.È. 2532 ¾º P53 ÃŒÍÂÅÐ 40-50 ¢Í§¼ÙŒ»†Ç ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ ʋǹãËÞ‹¾ºã¹¼ÙŒ»†ÇÂ

·ÕèÁÕ¡ŒÍ¹ÁÐàÃ秷ÕèÅÓäÊŒãËދʋǹ»ÅÒÂáÅзÇÒÃ˹ѡ

à¹×èͧ¨Ò¡ P53 äÁ‹ÁÕ¤ÇÒÁ¨Óà¾ÒШ֧äÁ‹ãªŒ P53 㹡Òà µÃǨ¤Ñ´¡Ãͧ ¡ÒáÓ˹´ÃÐÂТͧâä ËÃ×Í¡ÒõԴµÒÁ

¼ÙŒ»†ÇÂÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ¹⁴ ÃÐÂÐàÇÅÒ㹡Òà ÃÍ´ªÕÇÔµ¢Í§¼ÙŒ»†Ç·ÕèÁÕ P53 ໚¹ºÇ¡ËÃ×ÍźäÁ‹áµ¡µ‹Ò§¡Ñ¹ ᵋ¡ÒÃ㪌ÊÙµÃÂÒà¤ÁպӺѴ¾×鹰ҹ㹡ÒÃÃÑ¡ÉÒã¹¼ÙŒ»†ÇÂ

·ÕèÁÕ P53 ໚¹ÅºÊÒÁÒöà¾ÔèÁÃÐÂÐàÇÅÒÃÍ´ªÕÇԵ䴌¹⁵ Ras

¤Çº¤ØÁ¡ÒÃà¨ÃÔÞáÅСÒèÓṡÅѡɳÐ੾ÒТͧ

à«Åŏ â´Â¡Ãкǹ¡ÒÃÀÒ¹͡à«Åŏ ã¹»‚ ¾.È. 2541 ÁÕ¡ÅØ‹Á·Õè·Ó¡ÒÃÈÖ¡ÉÒàÃ×èͧ K-ras ã¹âäÁÐàÃç§

ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ (K-ras in Colorectal Cancer Collaborative Group: RASCAL study 1998) à¾×èÍ»ÃÐàÁÔ¹¤ÇÒÁÊÑÁ¾Ñ¹¸ÃÐËÇ‹Ò§¡ÒáÅÒ¾ѹ¸Ø

¢Í§ K-ras ¡Ñº¼Å¡ÒÃÃÑ¡ÉҢͧ¼ÙŒ»†Ç ¾ºÇ‹Ò¡Òà à»ÅÕè¹ÅӴѺ¨Ò¡¡ÅÑ«չ (glycine) ໚¹ÇÒÅÕ¹ (valine) ã¹â¤´Í¹·Õè 12 (Codon 12) ¢Í§ K-ras äÁ‹ä´Œà»š¹

»˜¨¨Ñ·Õè·ÓãËŒà¡Ô´¡ÒÃàÊÕªÕÇÔµ¹⁶ ¢ŒÍÁÙŨҡ¡ÒÃÈÖ¡ÉÒ

·Ò§¤ÅÔ¹Ô¡ã¹»˜¨¨ØºÑ¹¾ºÇ‹Ò K-ras ÁÕ¤ÇÒÁÊÑÁ¾Ñ¹¸¡Ñº

¡Òõͺʹͧµ‹ÍÂÒá͹µÔºÍ´Õé¡ÅØ‹Á anti-epidermal growth factor receptor (anti-EGFR) ã¹¼ÙŒ»†ÇÂâäÁÐàÃç§

ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡÃÐÂÐá¾Ã‹¡ÃШÒ Thymidylate synthase (TS)

à͹ä«Á¸ÑÂÁÔ´ÑÂàÅ·«Ô¹à¸Ê ໚¹à͹ä«Á·Õè໚¹à»‡ÒËÁÒ áÅк͡¶Ö§¡ÒþÂҡó¼Å¡ÒÃÃÑ¡ÉҢͧ 5-FU (5- fl uorouracil) à¹×èͧ¨Ò¡ 5-FU ¨ÐÂѺÂÑé§à͹ä«Á¸ÑÂÁÔ´ÑÂ- àÅ·«Ô¹à¸Ê㹡Ãкǹ¡ÒÃÊÌҧÊÒ¾ѹ¸Ø¡ÃÃÁ ¶ŒÒµÃǨ

¾ºÇ‹Ò¼ÙŒ»†ÇÂÁÕÃдѺà͹ä«Áª¹Ô´¹ÕéÊÙ§ ÂÒ 5-FU ¨ÐÍÍ¡Ä·¸Ôì ä´Œ´Õ¢Öé¹ ÃÐÂÐàÇÅÒÃÍ´ªÕÇÔµ¨Ð¹Ò¹¢Öé¹Í‹ҧÁÕ¹ÑÂÊÓ¤ÑÞ (p = 0.03)¹⁷

Thymidine phosphorylase (TP)

à͹ä«Á¸ÑÂÁÔ´Õ¹ ¿ÍÊâ¿ÃÑÂàÅÊ à»š¹ platelet derived endothelial cell growth factor ·Ó˹ŒÒ·Õè㹡ÒáÃе،¹

¡ÒÃà¨ÃÔޢͧà«ÅŏºØ¼¹Ñ§´ŒÒ¹ã¹¢Í§ËÅÍ´àÅ×Í´ «Öè§à¡ÕèÂÇ¢ŒÍ§

¡Ñº¡Ãкǹ¡ÒÃÊÌҧËÅÍ´àÅ×Í´¢Í§¡ŒÍ¹ÁÐàÃç§ ÃÇÁ·Ñé§

à»ÅÕè¹ 5-FU ãËŒÍÂÙ‹ã¹ÃÙ»·ÕèÍÍ¡Ä·¸Ôìä´Œ (tumor angio- genesis 5FU drug activation pathway) â´Â¾ºÇ‹Ò

¶ŒÒÁÕà͹ä«Á¸ÑÂÁÔ´Õ¹ ¿ÍÊâ¿ÃÑÂàÅÊ ÃÐÂÐàÇÅÒÃÍ´ªÕÇÔµ

¨Ðà¾ÔèÁÊÙ§¢Öé¹Í‹ҧÁÕ¹ÑÂÊÓ¤ÑÞ (p = 0.04)¹⁷

Dihydropyrimidine dehydrogenase (DPD)

DPD ໚¹à͹ä«Á·Õè¨Ó¡Ñ´ÍѵÃÒ¡ÒÃÊÅÒ¢ͧ 5-FU (rate-limiting enzyme in 5-FU catabolism) ·ÓãËŒ à»ÅÕè¹ 5-FU ä»ÍÂÙ‹ã¹ÃÙ»·ÕèäÁ‹ÍÍ¡Ä·¸Ôì ¼ÙŒ»†Ç·ÕèÁÕ DPD ¹ŒÍ¨Ðà¡Ô´¾Ôɵ‹Í 5-FU ÁÒ¡¢Öé¹

â´Â·ÑèÇ仡ÒÃà¡Ô´ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ·Õè à¡ÕèÂÇ¢ŒÍ§¡Ñº¡Òö‹Ò·ʹ·Ò§¾Ñ¹¸Ø¡ÃÃÁ ẋ§ä´Œà»š¹ 2 ª¹Ô´ ¤×Í

1. à¡Ô´¨Ò¡¡ÒÃÁÕÀÒÇÐäÁ‹àʶÕÂâͧâ¤ÃâÁâ«Á (chromosomal instability) ¾º»ÃÐÁҳÌÍÂÅÐ 85¹⁹ ÅѡɳÐà´‹¹ªÑ´¤×ÍÁÑ¡»ÃÒ¡¯ÃÍÂâä·Õ贌ҹ«ŒÒ¢ͧ

ÅÓäÊŒãËÞ‹ ¡ÒþÂҡóâääÁ‹´Õ¹Ñ¡ ÁÕ¡ÒáÅÒ¾ѹ¸Ø¢Í§

ÂÕ¹ P53 ¡ÒÃÃÑ¡ÉÒâ´Â¡ÒÃãËŒÂÒà¤ÁպӺѴËÇÁ¡Ñº 5-FU ã¹¼ÙŒ»†Ç¡ÅØ‹Á¹Õéä´Œ¼Å´Õ²⁰

2. à¡Ô´¨Ò¡¡ÒÃÁÕÀÒÇÐäÁ‹àʶÕÂâͧ´ÕàÍç¹àÍ·ÕèáÊ´§

ÅӴѺ¹ÔǤÅÕâÍä·´«éÓæ (microsatellite instability:

MSI) ¡ÒÃà¡Ô´ÁÐàÃç§ÅÓäÊŒãËÞ‹·Õèä´ŒÃѺ¡Òö‹Ò·ʹ·Ò§

¾Ñ¹¸Ø¡ÃÃÁ â´ÂÂÕ¹ MSI «Öè§ÂÕ¹ª¹Ô´¹Õé¨ÐÁÕ¹ÔǤÅÕâÍä·´

(nucleotides) «éÓæ ·ÕÅлÃÐÁÒ³ 1-5 ¹ÔǤÅÕâÍä·´

ÁÕ˹‹Ç«éӢͧàºÊ 2-7 ¤Ù‹àºÊ ¡ÒáÅÒ¾ѹ¸Øâ´Âà¡Ô´¡ÒÃàÅ×è͹ µÓá˹‹§àºÊ¢Í§´ÕàÍç¹àÍ仨ҡà´ÔÁ (frameshift muta- tions) ã¹µÓá˹‹§à©¾ÒÐ ¾º¡ÒÃà¡Ô´ÁÐàÃç§ÅÓäÊŒãËÞ‹áÅÐ

·ÇÒÃ˹ѡ»ÃÐÁҳÌÍÂÅÐ 15¹⁹ »ÃÒ¡¯ÃÍÂâä·Õ贌ҹ¢ÇÒ

¢Í§ÅÓäÊŒãËÞ‹ ¡ÒþÂҡóâä´Õ ¡ÒÃãËŒÂÒà¤ÁպӺѴ

àÊÃÔÁËÇÁ¡Ñº 5-FU äÁ‹¡‹ÍãËŒà¡Ô´»ÃÐ⪹ã¹¼ÙŒ‹»†Ç¡ÅØ‹Á¹Õé²⁰ MLH1, MSH2, MSH6

໚¹â»ÃµÕ¹·Õè·Ó˹ŒÒ·Õè㹡Òë‹ÍÁá«ÁÊÒ´ÕàÍç¹àÍ

·ÕèÁÕ¡ÒèѺäÁ‹µÃ§¤Ù‹àºÊ (mismatch repair: MMR protein)¹⁹ ÁÕʋǹà¡ÕèÂÇ¢ŒÍ§¡Ñº¡Òë‹ÍÁá«ÁÊÒ´ÕàÍç¹àÍ (DNA-repair) áÅСÒ÷ÓÅÒÂÊÒ´ÕàÍç¹àÍ (DNA damage) â´Â»¡µÔ MSH6 ¡Ñº MSH2 ¨Ð¨Ñº¡Ñ¹ áÅÐ

·Ó˹ŒÒ·ÕèàÊÁ×͹µÑǤÍÂÊʹʋͧÊÒ´ÕàÍç¹àÍ â´Â¶ŒÒ

¾ºÇ‹ÒÁÕ¤ÇÒÁ¼Ô´»¡µÔàÅ硹ŒÍ ¨ÐÃÇÁµÑǡѺ MLH1 áÅÐ㪌

¾Åѧ§Ò¹ adenosine triphosphate (ATP) ·ÓãËŒà¡Ô´¡ÒÃ

«‹ÍÁá«ÁÊÒ´ÕàÍç¹àÍ áµ‹¶ŒÒ¾º¤ÇÒÁ¼Ô´»¡µÔã¹ÊÒÂ

´ÕàÍç¹àͨӹǹÁÒ¡ «Ö觨оºä´Œã¹¡Ã³Õ¢Í§à«ÅŏÁÐàÃç§

MSH6 ¡Ñº MSH2 ¨Ð¨Ñº¡Ñº MLH1 â´ÂäÁ‹ãªŒ¾Åѧ§Ò¹ ATP ·ÓãËŒà¡Ô´Ç§¨Ãà«ÅŏËÂØ´ªÐ§Ñ¡ (cell cycle arrest)

¹Óä»ÊÙ‹¡ÒÃà¡Ô´¡Òë‹ÍÁá«Áʋǹ·ÕèÁÕ¡ÒÃàÊÕÂËÒÂáÅÐ

¡ÒÃÊÅÒÂà«Åŏ (apoptosis) ¢Í§à«ÅŏÁÐàÃ秢Öé¹ ´Ñ§¹Ñé¹ àÁ×è͵ÃǨ¾ºÇ‹Ò¼ÙŒ»†ÇÂÁÕ MSH6 áÅÐ MSH2 ãËŒ¼ÅºÇ¡

¨Ö§ÁÕ¡ÒþÂҡóâä·Õè´Õ²¹

Chromosome 18q-LOH/DCC (18q-loss of heterozygosity)

â¤ÃâÁâ«Á·Õè 18 ã¹Ê‹Ç¹¢Í§á¢¹ÂÒǵèÓá˹‹§·Õè 21

¨ÐÁÕµÑÇÃѺ¹ÔǵÃÔ¹ 1 (Neutrin-1 receptor) «Öè§ÁÕ˹ŒÒ·Õè 㹡ÒÃà¡Ô´¡Ãкǹ¡ÒÃÊÅÒÂà«Åŏ ¡ÒÃà¡ÒеԴ áÅÐÂѺÂÑé§

à«ÅŏÁÐàÃç§ (p = 0.0054) ã¹à«ÅŏÁÐàÃç§á¢¹¢Í§â¤ÃâÁâ«Á

¤Ù‹·Õè 18 ËÒÂä» 1 ¢ŒÒ§¨Ð·ÓãËŒà¡Ô´ loss of heterozygosity

·ÓãËŒäÁ‹ÊÒÁÒö·Õè¨Ð¡Ãе،¹ãËŒà¡Ô´¡Ãкǹ¡ÒÃÊÅÒ¢ͧ

à«Åŏ䴌 ´Ñ§¹Ñé¹à«ÅŏÁÐàÃ秨Ðà¾ÔèÁ¨Ó¹Ç¹ÊÙ§¢Öé¹àÃ×èÍÂæ

¨Ò¡¡ÒÃÈÖ¡ÉÒ¾ºÇ‹Ò ÁÕ¤ÇÒÁÊÑÁ¾Ñ¹¸¡Ñº¡ÒÃá¾Ã‹¡ÃШÒ 价ÕèµÑº «Öè§ã¹Í¹Ò¤µÊÒÁÒö㪌໚¹ÊÒú‹§ªÕéã¹Ê‹Ç¹¢Í§

âäÁÐàÃ秷ÕèÁÕ¡Òö‹Ò·ʹ·Ò§¾Ñ¹¸Ø¡ÃÃÁ¹

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»˜¨¨ØºÑ¹¹ÔÂÁÊ‹§µÃǨ CEA «Öè§à»š¹ÊÒú‹§ªÕé âäÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ à¾×èÍ㪌㹡Òà µÔ´µÒÁ¼Å¡ÒÃÃÑ¡ÉÒ ÃдѺ CEA ÊÑÁ¾Ñ¹¸¡Ñº¢¹Ò´

¢Í§¡ŒÍ¹à¹×éͧ͡㹼ٌ»†Ç·ÕèÃдѺ CEA »¡µÔ ᵋÁÕ ÃдѺ CA19-9 ¼Ô´»¡µÔ ¡ç¨Ð㪌 CA19-9 㹡Òà µÔ´µÒÁ¡ÒÃÃÑ¡ÉÒáÅСÒÃÅØ¡ÅÒÁ¢Í§âä ËÃ×Í¡ÒÃ

¡ÅѺ໚¹«éÓ ã¹»˜¨¨ØºÑ¹äÁ‹á¹Ð¹Óãˌ㪌ÊÒú‹§ªÕéÁÐàÃç§

ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡã´æ 㹡ÒõÃǨà¾×èͤѴ¡Ãͧ

¼ÙŒ»†ÇÂÁÐàÃç§ÅÓäÊŒãËÞ‹áÅзÇÒÃ˹ѡ

àÍ¡ÊÒÃ͌ҧÍÔ§

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