Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer.

BACKGROUND: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics. METHODS: Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.

Midday stomatal closure in Norway spruce--reactions in the upper and lower crown.

We used local microclimatic conditions and twig sap flow rates to interpret midday stomatal closure in the canopies of two 250-year-old Norway spruce (Picea abies (L.) Karst.) trees at a subalpine site in the Swiss Alps (1,650 m a.s.l.). Both trees showed midday stomatal closure on most clear summer days, despite the permanently wet soil. We used a modified Penman-Monteith formula to simulate potential transpiration of single twigs (ET(T)) based on high-resolution temporal and spatial microclimate data obtained both inside and outside the crowns. Comparison of calculated ET(T) values and measured twig sap flow rates enabled us to pinpoint the occurrence of midday stomatal closure and the microclimatic conditions present at that time. We found that vapor pressure deficit (and for upper-crown twigs, ET(T)) largely explained the timing of initial midday stomatal closure but gave no explanation for the different patterns of stomatal behavior after initial closure in upper- and lower-crown twigs. After the initial stomatal closure, upper-crown twigs maintained high transpiration rates by continuously regulating stomatal aperture, whereas stomatal aperture decreased rapidly in lower-crown twigs and did not increase later in the day. Midday stomatal closure in lower-crown twigs occurred on average 1 h later than in upper-crown twigs. However, the microclimate at the time of initial stomatal closure was similar at both crown locations except that lower-crown twigs received significantly less solar radiation than upper-crown twigs both at the time of initial stomatal closure and afterwards. High rates of sap flow in twigs did not always lead to stomatal closure and therefore could not explain the phenomenon. We conclude that stomatal conductance can be modeled accurately only when both local microclimatic conditions and tree water status are known. Further, we hypothesize that both the quantity and quality of light play an important role in the reopening of closed stomata during the day.

Reduced CD44 standard expression is associated with tumour recurrence and unfavourable outcome in differentiated thyroid carcinoma.

CD44 was detected with an antibody recognizing all forms of CD44 (CD44 standard) and others specific for its v3 and v6 variant isoforms; their prognostic value was evaluated in 213 patients with differentiated thyroid carcinoma (DTC). The staining patterns of CD44 standard (s) and CD44v6 in tumour tissue were quite similar, 176 cases (83%) being highly positive for CD44s and 153 cases (72%) for CD44v6. Only 18 (9%) tumours showed high expression of CD44v3. Papillary carcinomas were significantly more often high expressors of CD44s and CD44v6 than follicular carcinomas (p<0.001 for both). Age older than 60 years, distant metastases, and advanced pTNM stage were related to loss of expression of CD44s (p<0.001, p=0.021, and p=0.003, respectively). Tumour recurrence and cancer-related mortality were related to the reduced level of CD44s (p=0.049 and p=0.042). CD44v3 did not associate with any of the clinicopathological factors. In univariate analysis, CD44s was the only significant prognostic factor for disease-free survival (p=0.0488). In multivariate analysis, CD44s and thyroglobulin level were significant prognostic factors for disease-free survival (p=0.040 and p<0.001, respectively). The reduced level of CD44s in DTC patients seems to be an independent prognostic factor for unfavourable disease outcome.