Tumor size and proliferative marker geminin levels associated with SUVmax levels on PET for breast cancers

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67- high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Tumor size and proliferative marker geminin rather than Ki67 expression levels significantly associated with maximum uptake of 18F-deoxyglucose levels on positron emission tomography for breast cancers.

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67-high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes

Abstract Background Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. Methods A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. Results The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005–2.245 for CEA; HR 2.088, 95% CI 1.457–2.901 for CA15-3). Conclusions These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges

Comparison of SUVmax levels after combination of tumor size and geminin levels.

<p>SUVmax levels for groups with tumor size ≤2cm and geminin-low (G-L), ≤2cm and geminin-high (G-H), >2cm and geminin-low (G-L) and >2cm and geminin-high (G-H). Boxes represent median values and upper and lower quartiles.</p

Univariable and multivariable analyses of clinical and immunohistochemical factors for SUVmax levels.

<p>Univariable and multivariable analyses of clinical and immunohistochemical factors for SUVmax levels.</p

SUVmax levels according to tumor size and geminin expression levels.

<p>SUVmax levels according to tumor size and geminin expression levels.</p

Representative positive immunostaining for pS6 (A), pMAPK (B), TP53 (C) and geminin (D).

<p>Staining of cytoplasm (pS6), cytoplasm and nuclei (pMAPK) and nuclei (TP53 and geminin) was evaluated.</p

Correlations between SUVmax levels and pS6 (A), pMAPK (B), TP53 (C), geminin (D) or Ki67 (E) labeling indices and tumor size (F).

<p>Correlations between SUVmax levels and pS6 (A), pMAPK (B), TP53 (C), geminin (D) or Ki67 (E) labeling indices and tumor size (F).</p

Receiver operating characteristics curves of pS6, pMAPK, TP53, geminin and Ki67 for SUVmax.

<p>The cutoff values were determined as 10% for pS6 (A), 20% for pMAPK (B), 20% for TP53 (C), 4% for geminin (D) and 21.5% for Ki67 (E).</p