Abstract:
CONTEXT:Increased thymidylate synthase expression is a marker for decreased survival in colorectal cancer. OBJECTIVE:Thymidylate synthase localizes to both the nucleus and cytoplasm, but how the relationship of these expression levels affects colon cancer outcome has yet to be determined. DESIGN:Using AQUA, we assessed prognosis of thymidylate synthase expression as a function of subcellular localization in 2 retrospective cohorts of colorectal carcinoma. We used the first cohort (n = 599) as a training set, subsequently validating optimal expression cut points in the second cohort (n = 447). RESULTS:A significant association between decreased 5-year disease-specific survival and increased nuclear expression (16% decreased survival [72% to 56%] for the top 60% of nuclear-expressing tumors [P < .001]) and cytoplasmic expression (12% decreased survival [70% to 58%] for the top 54% of cytoplasmic-expressing tumors [P = .02]) was observed for the training set. A higher nuclear to cytoplasmic ratio also correlated significantly with decreased survival (15% decreased survival [66% to 51%] for the top 25% of tumors [P < .001]). Applying these findings to the validation set, as a function of time to recurrence, only the ratio (P = .03 [expression ratio]; P = .18 [nuclear]; P = .71 [cytoplasmic]) showed a significant association with decreased time to recurrence. Additionally, the expression ratio significantly added to the prognostic value given by the primary tumor pathologic classification and nodal status. CONCLUSIONS:These data suggest the relationship of nuclear to cytoplasmic thymidylate synthase expression, given as a ratio of continuous AQUA scores, to be a strong predictor of colon cancer survival.
journal_name
Arch Pathol Lab Medjournal_title
Archives of pathology & laboratory medicineauthors
Gustavson MD,Molinaro AM,Tedeschi G,Camp RL,Rimm DLdoi
10.1043/1543-2165-132.11.1746subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1746-52issue
11eissn
0003-9985issn
1543-2165pii
2007-0718-OAjournal_volume
132pub_type
杂志文章abstract::We report the clinical and postmortem findings in a newborn with Beckwith-Wiedemann syndrome and pulmonary hypoplasia. The infant was found to have a massively enlarged thymus gland that apparently caused pulmonary hypoplasia and respiratory insufficiency. Massive hyperplasia of the thymus gland should be considered i...
journal_title:Archives of pathology & laboratory medicine
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abstract::Since carcinomas of the colon or rectum are associated with blood loss, we wondered if complete blood count data were suggestive of iron deficiency in cases of colorectal carcinoma. The mean corpuscular volume and especially the red blood cell distribution width are thought to be more sensitive to early iron deficienc...
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