Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma.

PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America.

PURPOSE: Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS: All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. RESULTS: 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). CONCLUSIONS: ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

Circulating concentrations of leptin, ovarian follicle number, and oocyte lipid content and active mitochondria, in Zebu crossbred cows maintained on standard or improved nutrition.

Zebu (Bos indicus) crossbred beef cows (Droughtmaster) were maintained long-term (16 months) on standard nutrition (SN) or improved nutrition (IN). Cows on IN had better body condition and greater (P<0.05) circulating concentrations of leptin than cows on SN (0.7±0.1n/ml and 1.7±0.1n/ml, respectively). There were no outstanding differences between SN and IN cows in basal number of ovarian follicles (≤4mm, 5-8mm, and ≥9mm) and there were also no differences in number of oocytes recovered by oocyte pick-up. Cows on IN had a greater (P<0.05) number of total follicles after stimulation with FSH than cows on SN. Oocytes from cows on IN had greater (P<0.05) lipid content than cows on SN (-0.23±0.16 and 0.20±0.18 arbitrary units, respectively) and oocytes of the former cows also tended to have more active mitochondria, although this was not significant. Cows on IN showed a positive relationship (R(2)=0.31, P<0.05) between plasma leptin and oocyte lipid content. Lipids are utilized by oocytes during high energy consumptive processes including fertilization and early cleavage. The greater lipid content of oocytes from IN cows could therefore confer a reproductive advantage. The present study has shown relationships between nutrition, body condition, circulating leptin, and oocyte lipid content, but a clear cause-and-effect requires further investigation in the cow.

Behaviour of breast cancer molecular subtypes through tumour progression

INTRODUCTION Breast cancer (BC) becomes more aggressive throughout disease progression. Clinical stage is correlated with patient outcome. We hypothesised that BC molecular subtypes are associated with a poor prognosis in advanced clinical stages. We analysed the distribution and behaviour of molecular subtypes at different BC tumour size and variation of molecular subtype in recurrent lesions. PATIENTS AND METHODS: We studied 1647 consecutive patients with non-metastatic invasive and microinvasive (Tmi) BC treated from January 1997 to December 2007. Patients were categorised by tumour size and molecular subtype. A chi-square method was used for multiple group comparisons. Kaplan-Meier product limit method was used to calculate overall survival and disease-free survival. RESULTS: Median follow-up was 7.2 years. For patients with invasive BC the median age was 56 years. Four hundred and fifteen patients recurred and 225 died. Larger tumours were more frequently of triple-negative (TN) subtype than small ones or Tmi lesions. Any molecular subtype change from primary tumour to recurrent lesions is more likely to happen from a good prognosis to a subtype of worse prognosis than the opposite. Larger tumours of luminal A, luminal B and TN, but not HER2 subtype, are more likely to carry aggressive markers and to have worse outcomes than small ones. CONCLUSION: We found accumulation of TN subtype, migration to a poor prognosis subtype and increasing aggressiveness of luminal and TN subtypes throughout tumour progression. Tumours belonging to the HER2 subtype behave aggressively regardless of the primary size (AU)

The present and future of gene profiling in breast cancer.

Gene signatures can provide prognostic and predictive information to help in the treatment of early-stage breast cancer. Although many of these signatures have been described, only a few have been properly validated. MammaPrint and OncoType offer prognostic information and identify low-risk patients who do not benefit from adjuvant chemotherapy. With regard to prediction of response, molecular subtypes of breast cancer differ in their sensitivity to chemotherapy, although further studies are needed in this field. Cost, small sample size, and the need to use central laboratories are common limitations to the widespread use of these tools.