Отдаленные результаты лечения протоковой аденокарциномы

ÄççÄãõ ïàêìêÉàóÖëäéâ ÉÖèÄíéãéÉàà, 2004, ÚÓÏ 9, ‹ 1, Ò. 129–134
ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡
éÚ‰‡ÎÂÌÌ˚ ÂÁÛθڇÚ˚ ΘÂÌËfl ÔÓÚÓÍÓ‚ÓÈ
‡‰ÂÌÓ͇ˆËÌÓÏ˚ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚:
Ù‡ÍÚÓ˚, ‚ÎËfl˛˘Ë ̇ ÔÓ„ÌÓÁ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl
Ç. Ä. äÛ·˚¯ÍËÌ,
Ä. à. ô„Ó΂,
é. Ç. ŇÎÛÍÓ‚‡,
Ä. Ç. äÓ˜‡ÚÍÓ‚
éÚ‰ÂÎ ‡·‰ÓÏË̇θÌÓÈ
ıËÛ„ËË, è‡ÚÓÎӄӇ̇ÚÓÏ˘ÂÒÍÓ ÓÚ‰ÂÎÂÌË àÌÒÚËÚÛÚ‡
ıËÛ„ËË ËÏ. Ä.Ç. Ç˯Ì‚ÒÍÓ„Ó
(‰Ë. – ‡Í‡‰. êÄåç
Ç.Ñ. î‰ÓÓ‚) êÄåç
ㇷÓ‡ÚÓËfl „ÛÎflˆËË
ÍÎÂÚÓ˜Ì˚ı Ë ‚ËÛÒÌ˚ı
ÓÌÍÓ„ÂÌÓ‚ çàà ͇̈ÂÓ„ÂÌÂÁ‡,
êéçñ ËÏ. ç.ç. ÅÎÓıË̇
(‰Ë. – ˜ÎÂÌ-ÍÓ. êÄåç
å.à. ч‚˚‰Ó‚) êÄåç, åÓÒÍ‚‡
çÂÒÏÓÚfl ̇ ÒÓ‚ÂÏÂÌÌ˚ ‚ÓÁÏÓÊÌÓÒÚË Î˜ÂÌËfl ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚, ÔÓ„ÌÓÁ Ú˜ÂÌËfl ˝ÚÓ„Ó Á‡·Ó΂‡ÌËfl ÓÒÚ‡ÂÚÒfl Í‡ÈÌ Ì··„ÓÔËflÚÌ˚Ï.
ᇠÔÓÒΉÌË 10 ÎÂÚ ‚ àÌÒÚËÚÛÚ ıËÛ„ËË ËÏ. Ä.Ç. Ç˯Ì‚ÒÍÓ„Ó êÄåç ‚˚ÔÓÎÌÂÌÓ
57 Ô‡ÌÍ‡ÚÓ‰ÛÓ‰Â̇θÌ˚ı ÂÁÂ͈ËÈ ÔÓ ÔÓ‚Ó‰Û ÔÓÚÓÍÓ‚ÓÈ ‡‰ÂÌÓ͇ˆËÌÓÏ˚ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚. ë‰Ìflfl ÔÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË ·ÓθÌ˚ı ÒÓÒÚ‡‚Ë· 17.17 ± 1.68 ÏÂÒ., ωˇ̇ – 12 ÏÂÒ. èÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚ ÒÚ‡ÚËÒÚ˘ÂÒÍË ‰ÓÒÚÓ‚ÂÌÓ Á‡‚ËÒËÚ ÓÚ ÒÚ‡‰ËË ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡, ‡‰Ë͇θÌÓÒÚË ÓÔÂ‡ÚË‚ÌÓ„Ó ‚ϯ‡ÚÂθÒÚ‚‡, ÒÚÂÔÂÌË ‰ËÙÙÂÂ̈ËÓ‚ÍË
ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ. ç ‚˚fl‚ÎÂÌÓ ‚ÎËflÌËfl ‚‡ˇÌÚ‡ ‚˚ÔÓÎÌÂÌËfl Ô‡ÌÍ‡ÚÓ‰ÛÓ‰Â̇θÌÓÈ ÂÁÂ͈ËË (Ò ÒÓı‡ÌÂÌËÂÏ ÊÂÎۉ͇ ËÎË ÌÂÚ) ̇ ÓÚ‰‡ÎÂÌÌ˚ ÂÁÛθڇÚ˚ ΘÂÌËfl. Ç ÓˆÂÌÍ ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl ÔÂÒÔÂÍÚË‚Ì˚Ï ÔËÁ̇ÂÚÒfl ËÁÛ˜ÂÌË ‚
‰ËÌÓÏ ÔÓÚÓÍÓÎÂ Ò ÍÎËÌ˘ÂÒÍËÏË ‰‡ÌÌ˚ÏË Ë ·ËÓÎӄ˘ÂÒÍËı ı‡‡ÍÚÂËÒÚËÍ ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡.
Long Term Survival after Pancreatic Cancer Resection:
Factors of Prognosis
V. A. Kubishkin,
A. I. Shegolev,
O. V. Balukova,
A. V. Kotchatkov
Department of abdominal surgery,
Pathology department,
A.V. Vishnevsky Institute
of Surgery, RAMSei
Oncogine regulation laboratory,
Cancer Research Center,
RAMSci, Moscow
The prognosis of patients with pancreatic cancer is generally poor in spite of contemporary
treatment methods. We analyzed long term results of treatment of our patients for possible
prognostic factors in a retrospective trial.
57 patients (1993–2002) with histologically proven carcinoma of the head of the pancreas
underwent pancreatoduodenal resection in A.V. Vishnevsky Institute of surgery, RAMSci. The
mean and median survival time were 17.17 ± 1.58 and 12 months respectively. Stage of pancreatic cancer, the R0 status of the resection and histological grade had a significant influence
on the survival rate. A type of the partial pancreaticoduodenectomy had no correlation with
survival rate.
The prognosis for these patienst is determined not only by clinicopathologic staging, but also
tumor biology and molecular genetics factors. Developments in the broad field of molecular
genetics may improve our ability to predict long term survival of patients with pancreatic cancer.
ǂ‰ÂÌËÂ
Ç êÓÒÒËË ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÂÊ„ӉÌÓ Á‡·Ó΂‡ÂÚ ÓÍÓÎÓ 13 100 ˜ÂÎÓ‚ÂÍ [1]. ÑÎfl
˝ÚËı Ô‡ˆËÂÌÚÓ‚ ÔÓ„ÌÓÁ ÊËÁÌË Ô‰ÒÚ‡‚ÎflÂÚÒfl
‰ÓÒÚ‡ÚÓ˜ÌÓ ÒÂ¸ÂÁÌ˚Ï. ç‡ ÏÓÏÂÌÚ ÔÓÒÚ‡ÌÓ‚ÍË
Ô‡‚ËθÌÓ„Ó ‰Ë‡„ÌÓÁ‡ 80–85% ·ÓθÌ˚ı ÛÊ ÌÂÓÔÂ‡·ÂθÌ˚ ‚ Ò‚flÁË Ò ÏÂÒÚÌ˚Ï ËÎË ÓÚ‰‡ÎÂÌÌ˚Ï
‡ÒÔÓÒÚ‡ÌÂÌËÂÏ ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ [43].
ë‰Ìflfl ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË Ô‡ˆËÂÌÚÓ‚ Ò
ÌÂÂÁÂÍÚ‡·ÂθÌ˚Ï ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÒÓÒÚ‡‚ÎflÂÚ ÓÍÓÎÓ 6–7 ÏÂÒ. [31]. èflÚËÎÂÚÌflfl
‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ
ÊÂÎÂÁ˚ ÔÓÒΠ‡‰Ë͇θÌÓ„Ó ÓÔÂ‡ÚË‚ÌÓ„Ó Î˜ÂÌËfl, ÔÓ ‰‡ÌÌ˚Ï ‡Á΢Ì˚ı ÍÎËÌËÍ, Ô‰ÒÚ‡‚ÎÂ̇
‚ Ú‡·Î. 1.
낉ÂÌËfl Ó· ÓÚ‰‡ÎÂÌÌ˚ı ÂÁÛθڇڇı ΘÂÌËfl
‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ‰Ó‚ÓθÌÓ ‡ÁÌÓ˜˂˚. êfl‰ ‡‚ÚÓÓ‚ ÔË ÓˆÂÌÍ ÂÁÛθڇÚÓ‚ ΘÂ-
ÌËfl Û˜ËÚ˚‚‡˛Ú Ô‡ˆËÂÌÚÓ‚ Ò ‡Á΢Ì˚ÏË „ËÒÚÓÎӄ˘ÂÒÍËÏË ÙÓχÏË ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚, ˜ÚÓ Á‡‚˚¯‡ÂÚ ‰‡ÌÌ˚Â Ó ‚˚ÊË‚‡ÂÏÓÒÚË [34].
ÑÛ„Ë Ê ӈÂÌË‚‡˛Ú ÂÁÛθڇÚ˚ ΘÂÌËfl ÚÓθÍÓ ÔÓÚÓÍÓ‚ÓÈ ‡‰ÂÌÓ͇ˆËÌÓÏ˚ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ
ÊÂÎÂÁ˚ Í‡Í Ì‡Ë·ÓΠ˜‡ÒÚÓ ‚ÒÚ˜‡˛˘Â„ÓÒfl ÏÓÙÓÎӄ˘ÂÒÍÓ„Ó ‚‡ˇÌÚ‡ ÓÔÛıÓÎÂÈ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ [5]. éÚ‰‡ÎÂÌÌ˚ ÂÁÛθڇÚ˚ ΘÂÌËfl
‚ Ú‡ÍËı ËÒÒΉӂ‡ÌËflı Á̇˜ËÚÂθÌÓ ıÛÊÂ. í‡Í,
S. Nitecki Ë ÒÓ‡‚Ú. [30] ËÁ ÍÎËÌËÍË å‡ÛÓ ÔË ÍËÚ˘ÂÒÍÓÈ ÓˆÂÌÍ ÔÓÎÛ˜ÂÌÌ˚ı ÂÁÛθڇÚÓ‚ ÔÓ͇Á‡ÎË,
˜ÚÓ 5-ÎÂÚÌflfl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ÔÓÚÓÍÓ‚ÓÈ
‡‰ÂÌÓ͇ˆËÌÓÏÓÈ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ Ì 10%,
Í‡Í ·˚ÎÓ ÓÔÛ·ÎËÍÓ‚‡ÌÓ ‡Ì [38], ‡ 6.8%. èÓ ‰‡ÌÌ˚Ï ç‡ˆËÓ̇θÌÓÈ ·‡Á˚ ‰‡ÌÌ˚ı ·ÓθÌ˚ı ‡ÍÓÏ
ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ (National patterns of care
for pancreatic cancer) ëòÄ, 5-ÎÂÚÌflfl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ‡‰ÂÌÓ͇ˆËÌÓÏÓÈ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ
ÊÂÎÂÁ˚ ÔÓÒΠÓÔÂ‡ˆËË Ì Ô‚˚¯‡ÂÚ 4% [21].
129
9
ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡
éíÑÄãÖççõÖ êÖáìãúíÄíõ ãÖóÖçàü
퇷Îˈ‡ 1. éÚ‰‡ÎÂÌÌ˚ ÂÁÛθڇÚ˚ ‡‰Ë͇θÌÓ„Ó
ΘÂÌËfl ‡Í‡ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚
Ä‚ÚÓ
óËÒÎÓ
Ô‡ˆËÂÌÚÓ‚
èflÚËÎÂÚÌflfl
‚˚ÊË‚‡ÂÏÓÒÚ¸, %
û.à. è‡Ú˛ÚÍÓ Ë ÒÓ‡‚Ú., 2000 „.
23
0
P. Grace Ë ÒÓ‡‚Ú., 1986 „.
37
3.0
M. Connolly Ë ÒÓ‡‚Ú., 1987 „.
89
3.4
J. Lerut Ë ÒÓ‡‚Ú., 1984 „.
25
6.0
A. Cooperman, 1981 „.
70
7.0
B. Jones Ë ÒÓ‡‚Ú., 1985 „.
28
7.0
M. Sarr Ë ÒÓ‡‚Ú., 1993 „.
104
10.0
J. Klempnauer Ë ÒÓ‡‚Ú., 1996 „.
107
13.8
H. Baumel Ë ÒÓ‡‚Ú., 1994 „.
555
15.0
Y. Fong Ë ÒÓ‡‚Ú., 1995* „.
138
21.0
C. Yeo Ë ÒÓ‡‚Ú., 1999 „.
201
21.0
A. Richter Ë ÒÓ‡‚Ú., 2003** „.
122
25.4
R. Tsuchiya Ë ÒÓ‡‚Ú.,
1986*** „.
103
30.3
* 臈ËÂÌÚ˚ ‚ ‚ÓÁ‡ÒÚ ‰Ó 70 ÎÂÚ; ** Ô‡ˆËÂÌÚ˚, ÍÓÚÓ˚Ï
‚˚ÔÓÎÌÂÌÓ ‚ϯ‡ÚÂθÒÚ‚Ó ‚ Ó·˙ÂÏ R0; *** Ô‡ˆËÂÌÚ˚ Ò
ÓÔÛıÓθ˛ ‰Ó 2 ÒÏ.
[10, 45, 51]. ÇÎËflÌË ËÌÚ‡ÓÔÂ‡ˆËÓÌÌÓÈ „ÂÏÓÚ‡ÌÒÙÛÁËË Í‡Í Ò‡ÏÓÒÚÓflÚÂθÌÓ„Ó Ù‡ÍÚÓ‡ ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl ÔË ‡Í ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÔËÁ̇ÂÚÒfl Ì ‚ÒÂÏË ‡‚ÚÓ‡ÏË. S. Park
Ë ÒÓ‡‚Ú. [33] ÔË ‡Ì‡ÎËÁ ÓÚ‰‡ÎÂÌÌ˚ı ÂÁÛθڇÚÓ‚
ΘÂÌËfl 86 ·ÓθÌ˚ı ‡ÍÓÏ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ Ì ‚˚fl‚ËÎË ‡Á΢Ëfl ‚ ‚˚ÊË‚‡ÂÏÓÒÚË Ô‡ˆËÂÌÚÓ‚ ÌÂÁ‡‚ËÒËÏÓ ÓÚ Ôӂ‰ÂÌËfl Ò ËÌÚ‡ÓÔÂ‡ˆËÓÌÌÓÈ „ÂÏÓÚ‡ÌÒÙÛÁËÂÈ. çÂÁ‡‚ËÒËÏ˚Ï
ÔÓ„ÌÓÒÚ˘ÂÒÍËÏ Ù‡ÍÚÓÓÏ fl‚ÎflÂÚÒfl Ë ÔÎÓˉÌÓÒÚ¸ Ñçä ÍÎÂÚÓÍ ÓÔÛıÓÎË. ÄÌÂÛÔÎÓˉÌ˚È Ì‡·Ó ıÓÏÓÒÓÏ – ˝ÚÓ ÔÎÓıÓÈ ÔÓ„ÌÓÒÚ˘ÂÒÍËÈ ÔËÁ̇Í. ë‰Ìflfl ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË Ú‡ÍËı
·ÓθÌ˚ı ‰ÓÒÚÓ‚ÂÌÓ ÏÂ̸¯Â, ˜ÂÏ ÔË ‰ËÔÎÓˉÌÓÏ Ì‡·Ó ıÓÏÓÒÓÏ [8, 39, 36]. èÓ‚ÂʉÂÌËfl „ÂÌÓ‚-ÒÛÔÔÂÒÒÓÓ‚ p53, p16INK4 ÓÔ‰ÂÎfl˛Ú ̘ۂÒÚ‚ËÚÂθÌÓÒÚ¸ ÓÔÛıÓÎË Í ıËÏËÓÚÂ‡ÔËË Ë ÔÎÓıÓÈ
ÔÓ„ÌÓÁ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl. ïËÏËÓÚÂ‡Ô‚Ú˘ÂÒÍӠΘÂÌË ·ÓΠ˝ÙÙÂÍÚË‚ÌÓ Û ·ÓθÌ˚ı, ‚
ÓÔÛıÓÎflı ÍÓÚÓ˚ı Ì ‚˚fl‚ÎflÂÚÒfl ‡ÍÚË‚‡ˆËfl ÓÌÍÓ„Â̇ K-r‡s [3, 19, 28, 50].
Ç ‰‡ÌÌÓÏ ËÒÒΉӂ‡ÌËË ÔÓ‚Ó‰ËÚÒfl ÓˆÂÌ͇
‚ÎËflÌËfl ÍÓÏÔÎÂÍÒ‡ ÔÓ„ÌÓÒÚ˘ÂÒÍËı Ù‡ÍÚÓÓ‚
ÔË ‡Í ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚, ÍÓÚÓ˚È ‚Íβ˜‡ÂÚ ÍÎËÌ˘ÂÒÍËÂ, ÏÓÙÓÎӄ˘ÂÒÍËÂ Ë ÏÓÎÂÍÛÎflÌÓ-·ËÓÎӄ˘ÂÒÍË ı‡‡ÍÚÂËÒÚËÍË ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡.
å‡ÚÂË‡Î Ë ÏÂÚÓ‰
è˘ËÌÓÈ ÒÏÂÚË 97% ˝ÚËı Ô‡ˆËÂÌÚÓ‚ fl‚ÎflÂÚÒfl
ˆˉ˂ ÓÒÌÓ‚ÌÓ„Ó Á‡·Ó΂‡ÌËfl [42]. ÑÛ„ËÏË
ÒÎÓ‚‡ÏË, ËÁ 500 ·ÓθÌ˚ı ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ
ÊÂÎÂÁ˚ ‚˚ÔÓÎÌÂÌË ‡‰Ë͇θÌÓ„Ó Î˜ÂÌËfl ‚ÓÁÏÓÊÌÓ Û 100, ËÁ ÌËı 5-ÎÂÚÌËÈ Û·ÂÊ ‚ ÎÛ˜¯ÂÏ ÒÎÛ˜‡Â ÔÂÂÊË‚ÛÚ ÚÓθÍÓ ÌÂÒÍÓθÍÓ ˜ÂÎÓ‚ÂÍ.
Ç ÓÔ‰ÂÎÂÌËË ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl
̇˷Óθ¯Â Á̇˜ÂÌË ËÏÂ˛Ú ÒÚ‡‰Ëfl Á‡·Ó΂‡ÌËfl
(‡ÁÏÂ ÓÔÛıÓÎË, ÔÓ‡ÒÚ‡Ìˠ ‚ ÓÍÛʇ˛˘ËÂ
Ó„‡Ì˚ Ë Ú͇ÌË, ‚ ÚÓÏ ˜ËÒÎÂ Ë ÔÂËÌ‚‡Î¸Ì‡fl ËÌ‚‡ÁËfl, ÎËÏÙÓ„ÂÌÌÓÂ Ë „ÂχÚÓ„ÂÌÌÓ ÏÂÚ‡ÒÚ‡ÁËÓ‚‡ÌËÂ), ÓÒÓ·ÂÌÌÓÒÚË Î˜ÂÌËfl Ô‡ˆËÂÌÚÓ‚ (‡‰Ë͇θÌÓÒÚ¸ ÓÔÂ‡ÚË‚ÌÓ„Ó ‚ϯ‡ÚÂθÒÚ‚‡, Ó·˙ÂÏ
ÍÓ‚ÓÔÓÚÂË Ë „ÂÏÓÚ‡ÌÒÙÛÁËË, ‚ÓÁÏÓÊÌÓÒÚ¸
‚˚ÔÓÎÌÂÌËfl Îۘ‚ÓÈ ıËÏËÓÚÂ‡ÔËË), ÏÓÙÓÎӄ˘ÂÒÍË ı‡‡ÍÚÂËÒÚËÍË ÓÔÛıÓÎÂÈ Ú͇ÌË („ËÒÚÓÎӄ˘ÂÒÍËÈ ‚‡ˇÌÚ ÓÔÛıÓÎË, ÒÚÂÔÂ̸ ‰ËÙÙÂÂ̈ËÓ‚ÍË ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ) Ë ·ËÓÎӄ˘ÂÒÍË ÓÒÓ·ÂÌÌÓÒÚË ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ (ÔÎÓˉÌÓÒÚ¸ Ñçä
ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ, ÏÛÚ‡ˆËË ÓÔ‰ÂÎÂÌÌ˚ı „ÂÌÓ‚
Ë ‰.) [17, 26, 29, 32, 35, 42, 43, 48, 49].
êÓθ ÒÚ‡‰ËË ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ ‚ ÓÔ‰ÂÎÂÌËË ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÌÂÓ‰ÌÓÁ̇˜ÌÓ. Ç˚fl‚ÎÂÌË Á‡·Ó΂‡ÌËfl ̇
I ÒÚ‡‰ËË ÔÓ„ÌÓÒÚ˘ÂÒÍË ·Î‡„ÓÔËflÚÌÓ, ̇ IV· –
ÌÂÚ. èÓÚË‚Ó˜Ëfl ‚ ÓÔ‰ÂÎÂÌËË ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl ‚ÓÁÌË͇˛Ú ÔË II, III Ë IV‡ ÒÚ‡‰Ëflı. éÔÛ·ÎËÍÓ‚‡Ì˚ ‰‡ÌÌ˚Â, ҂ˉÂÚÂθÒÚ‚Û˛˘ËÂ
Ó· ÓÚÒÛÚÒÚ‚ËË ÔflÏÓÈ ÍÓÂÎflˆËË ÏÂÊ‰Û ÒÚ‡‰ËÂÈ
Ë ÔÓ„ÌÓÁÓÏ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl ‚ Ú‡ÍËı ÒÎÛ˜‡flı
130
ë 1993 ÔÓ 2002 „. ‚ ÓÚ‰ÂΠ‡·‰ÓÏË̇θÌÓÈ ıËÛ„ËË àÌÒÚËÚÛÚ‡ ıËÛ„ËË ËÏ. Ä.Ç. Ç˯Ì‚ÒÍÓ„Ó êÄåç ‚˚ÔÓÎÌÂÌÓ 57 Ô‡ÌÍ‡ÚÓ‰ÛÓ‰Â̇θÌ˚ı
ÂÁÂ͈ËÈ (èÑê) ·ÓθÌ˚Ï Ò ÏÓÙÓÎӄ˘ÂÒÍË ‚ÂËÙˈËÓ‚‡ÌÌÓÈ ÔÓÚÓÍÓ‚ÓÈ ‡‰ÂÌÓ͇ˆËÌÓÏÓÈ
„ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚. ëÚ‡‰ËË ÓÔÛıÓÎÂÈ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÓÔ‰ÂÎflÎË ÔÓ Í·ÒÒËÙË͇ˆËË TNM (UICC, 1997). ë‰ÌËÈ ‚ÓÁ‡ÒÚ
·ÓθÌ˚ı 57.9 ± 1.4 „Ó‰‡, ωˇ̇ – 60 ÎÂÚ. èÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ÎÂڇθÌÓÒÚ¸ ÒÓÒÚ‡‚Ë· 8.7%
(5 ·ÓθÌ˚ı). éÚ‰‡ÎÂÌÌ˚ ÂÁÛθڇÚ˚ ÔÓÒÎÂÊÂÌ˚ Û 52 Ô‡ˆËÂÌÚÓ‚: ÔflÏ˚Ï ÏÂÚÓ‰ÓÏ – Û
42(80.7%), ÊË‚˚ 6 (11.5%) Ô‡ˆËÂÌÚÓ‚, 1 Ô‡ˆËÂÌÚ
ÛÏÂ Ô‡ÍÚ˘ÂÒÍË Ò‡ÁÛ ÔÓÒΠ‚˚ÔËÒÍË ÓÚ ÒÓÔÛÚÒÚ‚Û˛˘Ëı Á‡·Ó΂‡ÌËÈ, 1 ·ÓθÌÓÈ ÛÏÂ ÓÚ ÓÒÚÓ„Ó ÍÓ‚ÓÚ˜ÂÌËfl ÔË ‡Á˚‚ ÒÂÎÂÁÂÌÍË ˜ÂÂÁ
5 ÏÂÒ ÔÓÒΠÓÔÂ‡ˆËË (̇ ‚ÒÍ˚ÚËË ÔËÁ̇ÍÓ‚ ˆˉ˂‡ ÓÒÌÓ‚ÌÓ„Ó Á‡·Ó΂‡ÌËfl Ì ‚˚fl‚ÎÂÌÓ).
ëÛ‰¸·‡ 2 (3.8%) Ô‡ˆËÂÌÚÓ‚ ÔÓÒÎÂÊÂ̇ ‚ Ú˜ÂÌËÂ
6 Ë 16 ÏÂÒ., ÔÓÒΠ˜Â„Ó Ò‚flÁ¸ Ò ÌËÏË ·˚· ÛÚÂfl̇.
ëÚ‡ÚËÒÚ˘ÂÒÍËÈ ‡Ì‡ÎËÁ ‰‡ÌÌ˚ı ÔÓ‚Ó‰ËÎÒfl Ò
ËÒÔÓθÁÓ‚‡ÌËÂÏ Ô‡ÍÂÚ‡ ÔÓ„‡ÏÏÌÓ„Ó Ó·ÂÒÔ˜ÂÌËfl “Statistica” (StatSoft, USA). ëÚ‡ÚËÒÚ˘ÂÒÍË ‰ÓÒÚÓ‚ÂÌÓÈ Ò˜ËÚ‡ÎË Á̇˜ÂÌË ÍÓ˝ÙÙˈËÂÌÚ‡ p < 0.05.
Ç˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚ ÓˆÂÌË‚‡ÎË Ò ËÒÔÓθÁÓ‚‡ÌËÂÏ ÏÂÚÓ‰‡ Kaplan–Meier.
êÂÁÛθڇÚ˚ Ë Ó·ÒÛʉÂÌËÂ
ë‰Ìflfl ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË ·ÓθÌ˚ı
ÔÓÒΠÓÔÂ‡ˆËË ÒÓÒÚ‡‚Ë· 17.17 ± 1.68 ÏÂÒ, ωˇ-
ÄççÄãõ ïàêìêÉàóÖëäéâ ÉÖèÄíéãéÉàà ÚÓÏ 9
‹1
2004
ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡
äÛ·˚¯ÍËÌ Ë ‰.
äÛÏÛÎflÚ˂̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚
(Cumulative Proportion Surviving)
äÛÏÛÎflÚ˂̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚
(Cumulative Proportion Surviving)
1.0
1.0
0.8
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0
6
12
18
24
30
36
42
48 54 60
ÇÂÏfl, ÏÂÒ
T2
T3
T4
6
0
12
18
24
30
36
42
48 54 60
ÇÂÏfl, ÏÂÒ
êËÒ. 1. Ç˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ‡ÍÓÏ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚, ÍÓÚÓ˚Ï ‚˚ÔÓÎÌÂÌÓ ‡‰Ë͇θÌÓ ÓÔÂ‡ÚË‚ÌӠΘÂÌË (Kaplan–Meier).
êËÒ. 2. èÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı
‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ
T-ÍËÚÂËfl (Kaplan–Meier).
̇ – 12 ÏÂÒ. êËÒ. 1 ËÎβÒÚËÛÂÚ ‚˚ÊË‚‡ÂÏÓÒÚ¸
·ÓθÌ˚ı ‡ÍÓÏ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚
ÔÓÒΠ‡‰Ë͇θÌÓÈ ÓÔÂ‡ˆËË.
èË ‡Ì‡ÎËÁ Á‡‚ËÒËÏÓÒÚË ÔÓÒÎÂÓÔÂ‡ˆËÓÌÌÓÈ
‚˚ÊË‚‡ÂÏÓÒÚË Ô‡ˆËÂÌÚÓ‚ ÓÚ ÍÎËÌ˘ÂÒÍËı ı‡‡ÍÚÂËÒÚËÍ ÓÔÛıÓÎË Ë Â ÚÂ‡ÔËË ‚˚fl‚ÎÂ̇ ‰ÓÒÚÓ‚Â̇fl Ò‚flÁ¸ ÒÓ ÒÚ‡‰ËÂÈ ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡, ‡‰Ë͇θÌÓÒÚ¸˛ Ò‡ÏÓ„Ó ÓÔÂ‡ÚË‚ÌÓ„Ó ‚ϯ‡ÚÂθÒÚ‚‡ Ë ÒÚÂÔÂ̸˛ ‰ËÙÙÂÂ̈ËÓ‚ÍË ÓÔÛıÓ΂˚ı
ÍÎÂÚÓÍ. ç ÓÚϘÂÌÓ ‚ÎËflÌËfl ‚‡ˇÌÚ‡ ‚˚ÔÓÎÌÂÌÌÓÈ èÑê (Ò ÒÓı‡ÌÂÌËÂÏ ÊÂÎۉ͇ ËÎË ÌÂÚ) ̇
ÔÓÒÎÂÓÔÂ‡ˆËÓÌÌÛ˛ ‚˚ÊË‚‡ÂÏÓÒÚ¸ (ÔÓ͇Á‡ÌËfl Í
‚˚ÔÓÎÌÂÌ˲ ‡Á΢Ì˚ı ‚ˉӂ èÑê ÒÏ. ‚ ÍÌË„Â
Ç.Ä. äÛ·˚¯ÍË̇ Ë Ç.Ä. Ç˯Ì‚ÒÍÓ„Ó [4]). á̇˜ÂÌË ÍÓ˝ÙÙˈËÂÌÚ‡ p ‰Îfl ˝ÚËı ÍËÚÂË‚ ÓˆÂÌÍË
Ô‰ÒÚ‡‚ÎÂÌ˚ ‚ Ú‡·Î. 2.
èË ÓˆÂÌÍ ı‡‡ÍÚÂËÒÚËÍ ÔÂ‚˘ÌÓÈ ÓÔÛıÓÎË, ‚ÎËfl˛˘Ëı ̇ ÔÓ„ÌÓÁ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl,
̇˷ÓΠ‚‡ÊÌ˚Ï Ô‰ÒÚ‡‚ÎflÂÚÒfl ‚ӂΘÂÌË ‚
ÓÔÛıÓ΂˚È ÔÓˆÂÒÒ ÂÚÓÔ‡ÌÍ‡Ú˘ÂÒÍÓÈ ÍÎÂÚ˜‡ÚÍË Ë Ï‡„ËÒÚ‡Î¸Ì˚ı ÒÓÒÛ‰Ó‚. ë‡ÏË ÔÓ Ò· ‡ÁÏÂ˚ ÓÔÛıÓÎË Ì Ó͇Á˚‚‡˛Ú ‰ÓÒÚÓ‚ÂÌÓ„Ó ‚ÎËflÌËfl ̇ ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË ÔÓÒΠÓÔÂ‡ˆËË
(p = 0.494). äÛÏÛÎflÚ˂̇fl ÔÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ T-ÍËÚÂËfl Ô‰ÒÚ‡‚ÎÂ̇
̇ ËÒ. 2.
ç‡Ë·ÓΠËÌÚÂÂÒÌÓ Ò‡‚ÌÂÌË ÓÚ‰‡ÎÂÌÌ˚ı
ÂÁÛθڇÚÓ‚ ΘÂÌËfl ·ÓθÌ˚ı ‡ÍÓÏ „ÓÎÓ‚ÍË
ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ̇ II Ë III ÒÚ‡‰Ëflı ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡. ùÚÓ ·ÓθÌ˚Â, Û ÍÓÚÓ˚ı ÓÔÛıÓθ ‡ÒÔÓÒÚ‡ÌflÂÚÒfl ̇ ‰‚Â̇‰ˆ‡ÚËÔÂÒÚÌÛ˛
Í˯ÍÛ, ÊÂΘÌ˚È ÔÓÚÓÍ, Ô‡‡Ô‡ÌÍ‡Ú˘ÂÒÍËÂ
Ú͇ÌË ÔË ÓÚÒÛÚÒÚ‚ËË ‚ӂΘÂÌËfl ÓÍÛʇ˛˘Ëı
Ó„‡ÌÓ‚ Ë Ï‡„ËÒÚ‡Î¸Ì˚ı ÒÓÒÛ‰Ó‚ (T3N0M0 –
II ÒÚ‡‰Ëfl) ËÎË ËϲÚÒfl ÎËÏÙÓ„ÂÌÌ˚ ÏÂÚ‡ÒÚ‡Á˚ (T1–3N1M0 – III ÒÚ‡‰Ëfl) ÔÓ Í·ÒÒËÙË͇ˆËË
åÂʉÛ̇Ó‰ÌÓ„Ó ÔÓÚË‚Ó‡ÍÓ‚Ó„Ó ÒÓ‚ÂÚ‡ (UICC)
1997 „. [41]. Ç ˝ÚÓÈ „ÛÔÔ ԇˆËÂÌÚÓ‚ ‰ÓÒÚÓ‚Â-
Ì˚ı ‡Á΢ËÈ ‚ ‚˚ÊË‚‡ÂÏÓÒÚË Ì ÔÓÎÛ˜ÂÌÓ (p =
= 0.345) (ËÒ. 3).
ç‡ ÓÒÌÓ‚‡ÌËË ÓÔ‰ÂÎÂÌËfl ÚÓθÍÓ ÒÚ‡‰ËË Á‡·Ó΂‡ÌËfl Ì‚ÓÁÏÓÊÌÓ ÔÓÎÛ˜ËÚ¸ Ô‰ÒÚ‡‚ÎÂÌËÂ
Ó ÚÂÏÔ‡ı ÓÒÚ‡ Ë ÔÓ„ÂÒÒËË ÓÔÛıÓÎË. í‡Í, ̇ÏË
Ì ÔÓÎÛ˜ÂÌÓ ÒÚ‡ÚËÒÚ˘ÂÒÍË ‰ÓÒÚÓ‚ÂÌÓÈ ÍÓÂÎflˆËË ÏÂÊ‰Û ÒÚÂÔÂ̸˛ ‰ËÙÙÂÂ̈ËÓ‚ÍË ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ Ë ÒÚ‡‰ËÂÈ ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ (‡ÁÏÂ‡ÏË ÔÂ‚˘ÌÓÈ ÓÔÛıÓÎË, ̇΢ËÂÏ ÎËÏÙÓ„ÂÌÌÓ„Ó ÏÂÚ‡ÒÚ‡ÁËÓ‚‡ÌËfl), ‡ Ú‡ÍÊ ‚ÓÁÏÓÊÌÓÒÚ¸˛
‚˚ÔÓÎÌÂÌËfl ‡‰Ë͇θÌÓ„Ó ÓÔÂ‡ÚË‚ÌÓ„Ó Î˜ÂÌËfl.
Ç ÚÓ Ê ‚ÂÏfl ËÏÂÂÚÒfl ‰ÓÒÚÓ‚Â̇fl Ò‚flÁ¸ ÏÂʉÛ
ÒÚÂÔÂ̸˛ ‰ËÙÙÂÂ̈ËÓ‚ÍË ÍÎÂÚÓÍ Ë ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸˛ ÊËÁÌË ÔÓÒΠÓÔÂ‡ˆËË (p = 0.0006)
(ËÒ. 4).
èÓÎÛ˜ÂÌÌ˚ ÂÁÛθڇÚ˚ „Ó‚ÓflÚ Ó ÌÂÓ·ıÓ‰ËÏÓÒÚË ÔÓËÒ͇ Ë ËÁÛ˜ÂÌËfl ‰ÓÔÓÎÌËÚÂθÌ˚ı ı‡‡ÍÚÂËÒÚËÍ ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ ‰Îfl ·ÓΠÚÓ˜ÌÓ„Ó ÓÔ‰ÂÎÂÌËfl ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl Û
ÍÓÌÍÂÚÌÓ„Ó Ô‡ˆËÂÌÚ‡. ë ˝ÚÓÈ ˆÂθ˛ ‚Ò ·Óθ¯ÂÂ
‚ÌËχÌË ۉÂÎflÂÚÒfl ËÁÛ˜ÂÌ˲ ·ËÓÎӄ˘ÂÒÍËı,
ÏÓÎÂÍÛÎflÌÓ-„ÂÌÂÚ˘ÂÒÍËı ı‡‡ÍÚÂËÒÚËÍ ‡Í‡
ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ [49, 50].
ä „Â̇Ï, ̇˷ÓΠ˜‡ÒÚÓ ‚Ó‚ÎÂ͇ÂÏ˚Ï ‚ ÔÓˆÂÒÒ Í‡ÌˆÂÓ„ÂÌÂÁ‡ ÔË ‡Í ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚, ÓÚÌÓÒflÚ ÓÌÍÓ„ÂÌ Ki-ras Ë ÓÔÛıÓ΂˚ ÒÛÔÂÒÒÓ˚ p53, p16INK4, DPC 4. èÓÚÓÓÌÍÓ„ÂÌ Ki-ras
ÄççÄãõ ïàêìêÉàóÖëäéâ ÉÖèÄíéãéÉàà ÚÓÏ 9
퇷Îˈ‡ 2. á̇˜ÂÌË ÍÓ˝ÙÙˈËÂÌÚ‡ p ÔË ÓˆÂÌÍÂ
ÍÓÂÎflˆËÓÌÌÓÈ Ò‚flÁË Ò ÔÓÒÎÂÓÔÂ‡ˆËÓÌÌÓÈ ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸˛ ÊËÁÌË
äËÚÂËÈ
p
í
0.016
LJˇÌÚ èÑê
0.169
ꇉË͇θÌÓÒÚ¸ (R)
0.04
ëÚÂÔÂ̸ ‰ËÙÙÂÂ̈ËÓ‚ÍË (G)
0.0006
‹1
2004
131
9*
ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡
éíÑÄãÖççõÖ êÖáìãúíÄíõ ãÖóÖçàü
äÛÏÛÎflÚ˂̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚
(Cumulative Proportion Surviving)
äÛÏÛÎflÚ˂̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ Ô‡ˆËÂÌÚÓ‚
(Cumulative Proportion Surviving)
1.0
1.0
II ÒÚ‡‰Ëfl
III ÒÚ‡‰Ëfl
0.8
0.6
0.6
0.4
0.4
0.2
0.2
0
6
12
18
24
30
36
42
ÇÂÏfl, ÏÂÒ
ëÚÂÔÂ̸
‰ËÙÙÂÂ̈ËÓ‚ÍË
ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ
0.8
0
‚˚ÒÓ͇fl
ÛÏÂÂÌ̇fl
ÌËÁ͇fl
6
12
18
24
30
36
42
48 54 60
ÇÂÏfl, ÏÂÒ
êËÒ. 3. èÓÒÎÂÓÔÂ‡ˆˆËÓÌ̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ
ÒÚ‡‰ËË Á‡·Ó΂‡ÌËfl (II–III ÒÚ‡‰ËË) (Kaplan-Meier).
êËÒ. 4. èÓÒÎÂÓÔÂ‡ˆËÓÌ̇fl ‚˚ÊË‚‡ÂÏÓÒÚ¸ ·ÓθÌ˚ı
‡ÍÓÏ „ÓÎÓ‚ÍË ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ‚ Á‡‚ËÒËÏÓÒÚË ÓÚ ÒÚÂÔÂÌË ‰ËÙÙÂÂ̈ËÓ‚ÍË ÓÔÛıÓ΂˚ı ÍÎÂÚÓÍ
(Kaplan-Meier).
‡ÒÔÓÎÓÊÂÌ Ì‡ ÍÓÓÚÍÓÏ ÔΘ ıÓÏÓÒÓÏ˚ 12, ‚
ÎÓÍÛÒ 13 (12p13) [23]. åÛÚ‡ˆËË ‚ ˝ÚÓÏ „ÂÌ ÔË‚Ó‰flÚ Í Â„Ó ‡ÍÚË‚‡ˆËË. ÑÎfl ÒÔÓ‡‰Ë˜ÂÒÍËı ÒÎÛ˜‡Â‚ ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ̇˷ÓΠı‡‡ÍÚÂÌ˚ ÏÛÚ‡ˆËË ‚ ÍÓ‰ÓÌ 12. ó‡ÒÚÓÚ‡ ‚˚fl‚ÎÂÌËfl
ÏÛÚ‡ˆËÈ Ki-ras ‚ ÍÓ‰ÓÌ 12 ÔË ‡Í ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÍÓηÎÂÚÒfl ÓÚ 47 ‰Ó 95% [23, 40, 47].
èË ‡Í ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ÏÛÚ‡ˆËfl Ki-ras
fl‚ÎflÂÚÒfl ‡ÌÌËÏ ÒÓ·˚ÚËÂÏ [15, 16, 27]. êfl‰ ‡‚ÚÓÓ‚ Ò˜ËÚ‡˛Ú, ˜ÚÓ ‡ÍÚË‚‡ˆËfl Ki-ras ‚ÓÁÏÓÊ̇ Ë
ÔË „ËÔÂÔ·ÒÚ˘ÂÒÍËı ÔÓˆÂÒÒ‡ı [27]. èÓ-‚ˉËÏÓÏÛ, ÏÛÚ‡ˆËfl Ki-ras ̇·Î˛‰‡ÂÚÒfl ÚÓθÍÓ ‚ ÚÂı
“‰Ó·Ó͇˜ÂÒÚ‚ÂÌÌ˚ı” ÔÓˆÂÒÒ‡ı, ‚ ÍÓÚÓ˚ı Í‡ÈÌ ‚˚ÒÓÍ ÔÓÚÂ̈ˇΠÁÎÓ͇˜ÂÒÚ‚ÂÌÌÓ„Ó ÔÂÂÓʉÂÌËfl. ç‡Î˘Ë ÏÛÚ‡ˆËÈ „ÂÌÓ‚ ras ÒÍÓ ‚Ò„Ó
Ò‚flÁ‡ÌÓ Ò ÔÓˆÂÒÒÓÏ Ú‡ÌÒÙÓχˆËË ÍÎÂÚÓÍ Ë ÌÂ
‚ÎËflÂÚ Ì‡ ÔÓÎËÙÂ‡ˆË˛ Ë ÒÔÓÒÓ·ÌÓÒÚ¸ ÍÎÂÚÓÍ Í
ÏÂÚ‡ÒÚ‡ÁËÓ‚‡Ì˲ [6]. ÉÂÌ p53 ÎÓ͇ÎËÁÓ‚‡Ì ‚
‡ÈÓÌ 17p13. îÛÌ͈ËË ·ÂÎ͇ p53 ‡ÁÌÓÓ·‡ÁÌ˚:
ÍÓÌÚÓθ Á‡ ÍÎÂÚÓ˜Ì˚Ï ˆËÍÎÓÏ, ‡ÔÓÔÚÓÁÓÏ, ÂÔ‡‡ˆËÂÈ Ñçä, ÍÎÂÚÓ˜ÌÓÈ ‰ËÙÙÂÂ̈ËÓ‚ÍÓÈ,
ÒÚ‡·ËθÌÓÒÚ¸˛ „ÂÌÓχ Ë ‰. [3]. íӘ˜Ì˚ ÏÛÚ‡ˆËË Ë ‰ÂΈËË ‚ „ÂÌ p53 ‰ÓÒÚ‡ÚÓ˜ÌÓ ı‡‡ÍÚÂÌ˚
‰Îfl ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ (40–80% ̇·Î˛‰ÂÌËÈ) Ë Ì ‚˚fl‚Îfl˛ÚÒfl ÔË ıÓÌ˘ÂÒÍÓÏ Ô‡ÌÍ‡ÚËÚ [37]. ï‡‡ÍÚÂÌÓ ‚˚Ô‡‰ÂÌË ӉÌÓ„Ó ÓÒÌÓ‚‡ÌËfl ‚ ˜ÂÚ‚ÂÚÓÏ ÍÓÌÒÂ‚‡ÚË‚ÌÓÏ ‰ÓÏÂÌ ·ÂÎ͇
(˝ÍÁÓ̇ı 5–9) [19, 40]. ÉÂÌ p16INK4 fl‚ÎflÂÚÒfl Ú‡ÍÊÂ
ÓÔÛıÓ΂˚Ï ÒÛÔÂÒÒÓÓÏ Ë ‡ÒÔÓÎÓÊÂÌ ‚ ÎÓÍÛÒÂ
9p21. ùÍÒÔÂÒÒËÛÂÏ˚È ËÏ ·ÂÎÓÍ Û˜‡ÒÚ‚ÛÂÚ ‚ „ÛÎflˆËË ÍÎÂÚÓ˜ÌÓ„Ó ˆËÍ· [3]. ÉÂÌ DPC 4 (Deleted
in Pancreatic Cancer) [ÒËÌÓÌËÏ Smad4] ‡ÒÔÓÎÓÊÂÌ
‚ 18q21. ÅÂÎÓÍ DPC 4 ‚˚ÔÓÎÌflÂÚ ‚‡ÊÌÛ˛ Óθ ‚
„ÛÎflˆËË ÔÂ‰‡˜Ë Ò˄̇· ‚ β-Ú‡ÌÒÙÓÏËÛ˛˘Â„Ó Ù‡ÍÚÓ‡ ÓÒÚ‡ [15]. DPC 4 Ë̇ÍÚË‚ËÓ‚‡Ì ‚
50–90% ̇·Î˛‰ÂÌËÈ ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚. èÓÚÂfl ÙÛÌ͈ËË „Â̇ ‚ 30% ÒÎÛ˜‡Â‚ Ò‚flÁ‡Ì‡ Ò
„ÓÏÓÁË„ÓÚÌ˚ÏË ‰ÂΈËflÏË, ‚ 20% – Ò ÔÓÚÂÂÈ „ÂÚÂÓÁË„ÓÚÌÓÒÚË ‚ ÍÓÏ·Ë̇ˆËË Ò ‚ÌÛÚÂÌÌÂÈ ÏÛÚ‡-
ˆËÂÈ ‚ÚÓÓ„Ó ‡ÎÎÂÎfl [23, 40]. èË “̇ÍÓÔÎÂÌËË”
‰ÓÒÚ‡ÚÓ˜ÌÓ ·Óθ¯Ó„Ó ˜ËÒ· ÏÛÚ‡ˆËÈ ‚ Íβ˜Â‚˚ı
„Â̇ı, Óڂ˜‡˛˘Ëı Á‡ ÊËÁ̉ÂflÚÂθÌÓÒÚ¸, ÚÂflÂÚÒfl ÒÔÓÒÓ·ÌÓÒÚ¸ ÍÎÂÚÍË ÔÓ‰‰ÂÊË‚‡Ú¸ ÒÚ‡·ËθÌÓÒÚ¸ „ÂÌÓχ Ë Óڂ˜‡Ú¸ ‡ÔÓÔÚÓÁÓÏ (Á‡ÔÓ„‡ÏÏËÓ‚‡ÌÌÓÈ „Ë·Âθ˛) ̇ ̇Û¯ÂÌËfl ‚ ÌÂÏ [2]. ùÚÓ
fl‚ÎflÂÚÒfl Ô‰ÔÓÒ˚ÎÍÓÈ Í ËÁÏÂÌÂÌ˲ ÔÎÓˉÌÓÒÚË
Ñçä ÍÎÂÚÓÍ. ó‡ÒÚÓÚ‡ ‡ÌÂÛÔÎÓˉËÈ ‚ ÍÎÂÚ͇ı ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ Û‚Â΢˂‡ÂÚÒfl ÔÓ ÏÂ ÓÔÛıÓ΂ÓÈ ÔÓ„ÂÒÒËË Ë ‚‡¸ËÛÂÚ ÓÚ 10 ‰Ó
79%. èË ËÒÒΉӂ‡ÌËË ÒÓ‰ÂʇÌËfl Ñçä ‚ ÍÎÂÚ͇ı ÓÔÛıÓÎË ÌÂÓÔÂ‡·ÂθÌ˚ı ·ÓθÌ˚ı ÔÓˆÂÌÚ
‡ÌÂÛÔÎÓˉÌ˚ı ÓÔÛıÓÎÂÈ ÒÓÒÚ‡‚ÎflÂÚ 55–75 [36, 39].
Ç Ì‡ÒÚÓfl˘Â ‚ÂÏfl ̇ÏË ÔÓ‚Ó‰ËÚÒfl ËÒÒΉӂ‡ÌË ‚ÎËflÌËfl ÏÓÎÂÍÛÎflÌÓ-„ÂÌÂÚ˘ÂÒÍËı ı‡‡ÍÚÂËÒÚËÍ, Ú‡ÍËı Í‡Í ÔÎÓˉÌÓÒÚ¸ Ñçä ÓÔÛıÓ΂˚ı
ÍÎÂÚÓÍ, ÔÓÚÂfl „ÂÚÂÓÁË„ÓÚÌÓÒÚË ÎÓÍÛÒÓ‚ ‡ÒÔÓÎÓÊÂÌËfl „ÂÌÓ‚ p16INK4, DPC 4 Ë ÏÛÚ‡ˆËÈ „ÂÌÓ‚
Ki-ras (ÍÓ‰ÓÌ 12) Ë p53 (ÍÓ‰ÓÌ˚ 273, 249, 157), ̇
ÔÓÒÎÂÓÔÂ‡ˆËÓÌÌÛ˛ ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸ ÊËÁÌË
·ÓθÌ˚ı ‡ÍÓÏ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚. è‰‚‡ËÚÂθÌ˚ ‰‡ÌÌ˚ ˝ÚÓ„Ó ËÒÒΉӂ‡ÌËfl ÔÓÁ‚ÓÎfl˛Ú ÓÚÏÂÚËÚ¸ ÌÂÍÓÚÓ˚ ÚẨÂ̈ËË. åÛÚ‡ˆËË „Â̇
Ki-ras ‚˚fl‚Îfl˛ÚÒfl ‚ 60% ̇·Î˛‰ÂÌËÈ. èÓÚÂfl „ÂÚÂÓÁË„ÓÚÌÓÒÚË „Â̇ DPC 4 ‚˚fl‚ÎflÂÚÒfl ̇ ÔÓÁ‰ÌËı ÒÚ‡‰Ëflı Ë ‡ÒÒÓˆËËÓ‚‡Ì‡ Ò Ì·Óθ¯ÓÈ ÔÓ‰ÓÎÊËÚÂθÌÓÒÚ¸˛ ÔÓÒÎÂÓÔÂ‡ˆËÓÌÌÓÈ ÊËÁÌË Ô‡ˆËÂÌÚÓ‚.
í‡ÍËÏ Ó·‡ÁÓÏ, ÓÔ‰ÂÎÂÌË ÒÚ‡‰ËË ‡Í‡ ÔÓ‰ÊÂÎÛ‰Ó˜ÌÓÈ ÊÂÎÂÁ˚ ̇ ‚ÒÂı ˝Ú‡Ô‡ı Θ·ÌÓ„Ó
ÔÓˆÂÒÒ‡ ÌÂÓ·ıÓ‰ËÏÓ ‰Îfl ‚˚·Ó‡ ‡‰ÂÍ‚‡ÚÌÓÈ Ú‡ÍÚËÍË ‚‰ÂÌËfl ÍÓÌÍÂÚÌÓ„Ó Ô‡ˆËÂÌÚ‡ Ë ÓÔ‰ÂÎÂÌËfl ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl Á‡·Ó΂‡ÌËfl. àÁÛ˜ÂÌËÂ
Ù‡ÍÚÓÓ‚, ‚ÎËfl˛˘Ëı ̇ ÔÓ„ÌÓÁ Á‡·Ó΂‡ÌËfl, ÔÓ͇Á˚‚‡ÂÚ ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‰ÂڇθÌÓ„Ó ËÁÛ˜ÂÌËfl
‡ÒÔÓÒÚ‡ÌÂÌÌÓÒÚË ÓÔÛıÓÎÂ‚Ó„Ó ÔÓˆÂÒÒ‡ ̇ ÂÚÓÔ‡ÌÍ‡Ú˘ÂÒÍÛ˛ ÍÎÂÚ˜‡ÚÍÛ Ë Ï‡„ËÒÚ‡Î¸Ì˚Â
ÒÓÒÛ‰˚, ÎËÏÙÓ„ÂÌÌÓ„Ó ÏÂÚ‡ÒÚ‡ÁËÓ‚‡ÌËfl. èÂÒÔÂÍÚË‚Ì˚ÏË ÔËÁ̇˛ÚÒfl ËÒÒΉӂ‡ÌËfl, ̇Ô‡‚-
132
ÄççÄãõ ïàêìêÉàóÖëäéâ ÉÖèÄíéãéÉàà ÚÓÏ 9
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ÔÓ‰ÊÂÎۉӘ̇fl ÊÂÎÂÁ‡
äÛ·˚¯ÍËÌ Ë ‰.
ÎÂÌÌ˚ Ì ÚÓθÍÓ Ì‡ ËÁÛ˜ÂÌË ÍÎËÌ˘ÂÒÍËı ‰ÂÚÂÏË̇ÌÚ ÔÓ„ÌÓÁ‡ Ú˜ÂÌËfl ·ÓÎÂÁÌË, ÌÓ Ë Ì‡ ÔÓËÒÍ ·ËÓÎӄ˘ÂÒÍËı ı‡‡ÍÚÂËÒÚËÍ, ÍÓÚÓ˚ ‰‡˛Ú
Ô‰ÒÚ‡‚ÎÂÌËÂ Ó ÁÎÓ͇˜ÂÒÚ‚ÂÌÌÓÏ ÔÓÚÂ̈ˇÎÂ
ÓÔÛıÓÎË.
ëÔËÒÓÍ ÎËÚÂ‡ÚÛ˚
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