The dissemination of a malignant neoplasia is a complex process, which requires a set of molecules that remains unknown. It has been suggested that mucins and their carbohydrate-associated antigens may be implicated in tumour spreading which may be also influenced by an anti-MUC1 immune response. In this pilot study, we report the pattern of carbohydrate and peptidic MUC1-associated epitopes on carcinoma cells isolated from bone marrow (BM), taking into account primary tumour histopathologic features. We also bring information about the anti-MUC1 humoral response in these patients. Seventeen patients with invasive breast carcinoma were included. A sample of the primary tumour, a serum sample and a BM aspirate were obtained from each patient. Clinical features studied were tumour size, number of metastatic nodes, histological type and disease stage. Standard immunohistochemistry was performed with antigenic retrieval using different monoclonal antibodies (MAbs): anti carbohydrate antigens: Lewis x (KM380), sLewis x (KM93), Lewis y (C14) and Tn, anti-MUC1 peptide core MAbs: C595, HMFG2 and SM3, anti-cytokeratins, anti-protoncogenes ErbB2 and ErbB3 (IgG) MAbs and also anti-CD34 and anti-CD45 MAbs. ELISA techniques were employed to study circulating MUC1 as well as free and complexed anti-MUC1 antibodies. Immunohistochemical results showed that carbohydrate antigenic expression increases in BM neoplastic cells compared to the original tumours. However, we were not able to demonstrate that a humoral immune response to MUC1 has been induced in these patients. Finally, the employed procedures allow the selective immortalisation of micrometastatic carcinoma cells since short-term cell lines were established.
The expression of three lineage specific antigens in the leukemic blasts is extremely infrequent. We here report a case of triphenotypic acute leukemia with involvement of the myeloid and B and T lineages. The morphology of the blasts showed promyelocytic features with agranular cytoplasm, suggesting a M3-variant of AML. The blasts were positive for myeloperoxidase PAS and Sudan Black. Immunophenotype and cytogenetics did not confirm M3-AML diagnosis, showing a trilineage compromise (myeloid and T and B lymphoid markers) and the cytogenetic alterations +8 and +11, respectively. This report highlights the importance of correlating the results of multiple diagnostic methods in order to establish a correct diagnosis of mixed lineage acute leukemias, and allows evaluation of the prognostic importance of this subgroup of patients.
Background: The study of sentinel lymph node (SNL) assessed by OSNA provides a new variable, Total Tumoral Load (TTL).This variable is defined as the amount of CK19 mRNA copies number in all positives SLN. TTL has been showed to predict the axillary node status and has been analysed to determine its usefulness in the axillary surgical management. Based on TTL values different cut-off points have been proposed (last 25.000 copies) to establish a new tool to practice axillary lymph node dissection (ALND). We present the follow-up data of at least 5 years of breast cancer patients who underwent ALND according, strictly, to Z0011 trial criteria. We hypothesized that there will be no correlation between TTL and locoregional relapse if Z0011 are followed. Methods: Clinicopathological and follow up data were obtained from patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2012 at Complejo Asistencial de Ávila, Spain. ALND was decided based on Z0011 study criteria independently of TTL. All patients have been followed for a minimun of 5 years. Results: A total of 106 patients underwent SN assessed by OSNA, age range 27-85 years (mean 58,96). Of them 90% were ductal, 7,5% lobular and 2% others. By inmunophenotype: Luminal A 55%, Luminal B 28%, Triple Negative 9,4%, Her2 positive 3,7% and Luminal B-Her2 positive 2,8%. TTL was equal to zero in 58 cases and greater than zero in 48 cases with a range of 280-2.700.000 copies. Only 5 cases met ALND criteria (average TTL 68.164). Average TTL in cases without ALND was 111.000. For the time being, none of them has had locoregional relapse (median follow up 65 months). 3 patients have died one metastatic desease (Negative SN), one uterine cervix cancer and one neutropenic fever. Baseline and outcomes dataVARIABLE N%Age, years (median, range) 59 (27-85) Tumour TypeDuctal9690,5 Lobular87,5 Others21,8InmunophenotypeLuminal A5955,6 Luminal B3028,3 Luminal B-Her232,8 Her243,7 Triple Negative109,4Total Tumoral Load (TTL)=05854,7 >04845,2Axillary Lymph Node Dissection (ALND) 254,7TTL >25.000 2321,7Locoregional relapse 00Overall Survival 95,2 Conclusions: -Using Z0011 criteria and OSNA no locoregional recurrence has been observed so far. -TTL did not predict risk of recurrence -If we had based axillary management only on TTL values (i.e higher than 25.000 copies) we would have unnecessarily increased the number of lymphadenectomies in a 22%. This is an ongoing study that designed to increased the sample size and obtain longer follow-up data. Citation Format: Tur R, De Grado C, Martin MR, De Castro J, Filipovich E, Segovia B, Ceballos J, Parra J, Revestido R, Alés-Martínez JE. Relationship of axillary total tumor load (TTL) by OSNA (one step nucleic acid amplification) in early breast cancer and clinical outcomes using strict Z0011 study criteria for axilla management [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-19.
BACKGROUND: Factors by which breast cancer cells invade blood and lymphatic capillaries and metastasize regional lymph nodes and distant sites are not well understood. Genetics, molecular subtype, epidemiological, mechanical and pathological factors are being considered. Once breast cancer cells invade lymphatic or blood vessels the route of spread is still unclear. Cells could access the systemic circulation through the sentinel lymph node or directly avoiding the lymph node step. Molecular subtype is one of the most important factors associated with the risk of metastases. Our objective is to determine the influence of immunophenotype and the sentinel lymph node (SLN) status to predict the risk of locoregional relapses and distant metastases in early breast cancer. In our center we are using a molecular technique (OSNA) to ascertain if there is sentinel lymph node involvement, this technique creates a new continuous variable, Total Tumor Load (TTL), defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL), indicating the total tumor volume of axillary tumor involvement. METHODS: Clinicopathological and follow up data were obtained from all patients with early breast cancer treated with Tumorectomy (Tx) and Sentinel Lymph Node (SLN) assessed by OSNA with the decision to proceed to ALND based on Z0011 criteria and systemic therapy between 2011 and 2018 at our center (J Clin Oncol 37, 2019 (suppl; abstr 564)) RESULTS: 304 breast cancer patients underwent Tx and SLN assessed by OSNA followed by systemic therapy with an average follow-up of 64.9 months. SLN was positive in 122 cases and negative in 182. SLN negative patients were Luminal A (LA) 58%, Luminal B (LB) 14%, HER2 10% and Triple-Negative (TN) 7%. SLN positive patients were LA 52%, LB 35%, HER2 7% and TN 5%. Mean TTL was 136,244 copies (see table). As of now, 11 patients have had recurrence (locoregional relapse and distant disease): 6 of them with positive SLN (54,54%) and 5 with negative SLN (45,45%). A total of 4 patients have had locoregional relapse, two of them with negative SLN (50%) both non luminal tumors (1 HER2, 1 TN), and 7 have had distant disease, three of them with negative SLN (43%). Only one patient has died from metastatic breast cancer (HER2 positive, SLN negative). CONCLUSIONS: 1. In our series, almost half of the patients (45%) with recurrence were negative SLN. 2. The probability of recurrence when the sentinel lymph node is negative is higher in HER2 and TN tumors (60%). 3. The probability of recurrence when the SLN is positive is higher in luminal tumors (66,6%). 4. Luminal tumors with positive SLN and large volume axillary involvement (median 1.419.450 copies) have a higher probability of recurrence (statistically significant) than luminal tumors with positive SLN and small volume axillary involvement (median 131.479 copies). PATIENTS AND OUTCOMES VARIABLE N=304Number of cases (n,%)Median age, range (years)LOCOREGIONAL RELAPSEMETASTASIC BREAST CANCEREXITUSMean TTL with NO recurrenceMean TTL with recurrencePOSITIVE SLN122 (40%)59,8 (33-87)2 (1,63%)4 (3,27%)0By ImmunophenotypeLuminal A64 (52,4%)59,3 (36-87)1 (1,5%)2 (3,1%)0371.5592.838.333Luminal B43 (35,2%)59,5 (36-84)1 (2,32%)00258.6221600HER29 (7,3%)61 (33-80)01 (11,1%)021.582640Triple Negative6 (5%)59,6 (50-80)01 (16,6%)0108.181184.000NEGATIVE SLN182 (60%)59,3 (27-89)2 (1,09%)3 (1,64%)1 (0,5%)By ImmunophenotypeLuminal A106 (58%)59,3 (33-82)000Luminal B43 (14,1%)59,5 (36-89)1 (2,32%)1 (2,32%)0HER219 (10,4%)59,3 (40-82)01 (5,2%)1 (5,2%)Triple Negative14 (7,7%)59,4 (27-85)1 (7,14%)1 (7,14%)0 Citation Format: José Enrique Alés-Martínez, Raquel Tur, Juan Parra, Ana De Castro, Jaime Ceballos, Rocío Martín, Rosa Ana Marcos, Paz Blanco, MJose Velasco. Cancer phenotype is the key factor in axillary involvement and distant recurrence in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-03.
BACKGROUND The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. METHODS Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and end of 2016 at our center. RESULTS A total of 277 patients underwent SNB assessed by OSNA with an average follow-up of 56.4 months. 276 were female and 1 male. Age range 27-88 years (mean 58,7). 86,2 % were ductal, 10,8 % lobular and 2,8 % other. 51.9% were luminal A, 51.98% luminal B, 28.51%, triple negative, 5% Her2 positive and 5% luminal B-Her2 positive. TTL was equal to 0 in 155 cases and greater than zero in 122 cases.68 cases showed a TTL higher than 15,000 copies. Only 19 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse (TTL = 0 in 2 cases and 18,000 copies in one) and 5 metastatic disease (none with simultaneous locoregional recurrence). 7 patients have died (one from metastatic breast cancer, 1 febrile neutropenia, 2 septic shock unrelated to chemotherapy, 2 from other tumors, 1 encephalopathy). BASELINE DATA N=277VARIABLE N%AGE,MEDIAN RANGE 58,7 (27-88) TUMOR TYPEDuctal23986,2 Lobular3010,8 Others82,8IMMUNOPHENOTYPELuminal A14451,98 Luminal B7928,51 Luminal B-HER2145 HER2 positive14 Triple Negative269,3TOTALL TUMORAL LOAD (TTL)=015556 >012244AXILLARY LYMPH NODE DISECTIONS 196,8TTL>15000 6824,5LOCOREGIONAL RELAPSES 31 CONCLUSIONS 1. Using Z0011 criteria, we have adequate clinical outcomes with a very low rate of ALND and locoregional recurrences. 2. If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 2,7 (from 18 to 50). 3. We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes. 4. Work is in progress to increase our sample size. Citation Format: Tur R, Parra J, Martin R, Alés-Martinez JE. No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-17.
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