Diagnosis of micrometastasis in muscle invasive bladder cancer through immunohistochemistry analysis: is there indication for routine evaluation?

Background: Muscle invasive bladder cancer (BC) has a mortality rate of 50% in 5 years, despite the aggressive treatments currently used. The diagnosis of latent tumor cells in histologically normal lymph nodes (LN) may have prognostic value and may explain the tumoral recurrence in BC. Methods: Here we evaluated the use of the AE1AE3 cytokeratin marker through immunohistochemical examination of LNs to diagnose micrometastasis in patients with BC undergoing radical cystectomy (RC) and lymph node dissection. Sixty-one patients with pN0 diseases who were submitted to RC were studied. Conventional histological evaluation indicated that these patients did not have lymph node metastasis. Histological sections were reviewed and analyzed by immunohistochemistry (IHC) using the AE1AE3 antibody in single sections. Results: The total number of removed LNs was 832, averaging 13.64 LNs per patient. The IHC evaluation revealed that LN from 2/61 (3.27%) patients had micrometastasis. At the time of the last follow-up, 41% of all patients were in complete disease remission and 41.1% had died from BC. Conclusions: Our study shows that histological analysis using hematoxylin eosin (HE) method by experienced pathologists is sufficient for the diagnosis of LN metastasis and, therefore, there is no indication for routine IHC evaluation in patients at histopathological pN0 stage. (AU)

Detection of CK19, LUNX, and KS1/4 mRNA expression in the peripheral blood for diagnosis of micrometastases in patients with non-small cell lung cancer and their clinical implications.

The expression of CK19, LUNX, and KS1/4 mRNA biomarkers was detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients to investigate the feasibility of indicating lung cancer micrometastases. Micrometastases were identified in the peripheral blood of 32 NSCLC patients, 15 benign pulmonary disease (BPD) patients, and 10 healthy volunteers by reverse transcriptase-polymerase chain reaction. The detection rates of CK19, LUNX, and KS1/4 mRNA-positive cells in the peripheral blood obtained from the NSCLC group were 34.4% (11/32), 37.5% (12/32), and 25% (8/32), respectively. CK19, LUNX, and KS1/4 mRNA-positive cells were detected in 6.6% (1/15), 0.0% (0/15), and 13.3% (2/15) of the patients with BPD, respectively. However, the healthy group did not express any of the three markers. The expression of CK19, LUNX, and KS1/4 mRNA was significantly higher in the NSCLC group than that in the healthy and BPD groups (P < 0.05). CK19 and LUNX mRNA may be ideal biomarkers indicating micrometastases in patients with NSCLC; however, the diagnostic applicability of KS1/4 mRNA remains uncertain. The rate of expression of CK19 was not correlated with the clinicopathological characteristics (P > 0.05). The rate of expression of LUNX and KS1/4 was closely related to the clinical stage (P < 0.05), and not related to the clinical characteristics of the disease (age, gender, smoking history, pathological type, histologic classification, and differentiation; P > 0.05).

[Micrometastases: strategies for detection]. / Micrometástasis: estrategias para su detección.

Micrometastasis or minimal residual disease has become critically important in oncology since it represents a true clinical problem that must be solved, as the response of these tumor foci to the different treatments that are used for the control of cancer, is still unknown. Even though this is a fundamental specific problem to be solved, there are already immunohistochemical and molecular biology diagnostic methods that have allowed microfoci location of tumor cells in various organs and tissues, and different techniques are available to determine and quantify these lesions. Within these techniques, flow cytometry and different molecular methods are included, and they range from the traditional to the newest and most sophisticated. The goal of this review was aimed to evaluate new diagnostic methods that permit the identification of this residual disease, which would serve to establish individualized treatments and prevent the recurrence of the disease in cancer patients under treatment.

Micrometástasis: estrategias para su detección / Micrometastases: strategies for detection

La micrometástasis o enfermedad mínima residual ha adquirido una importancia trascendental en oncología al representar un verdadero problema clínico que debe ser solucionado, ya que aún se desconoce la respuesta de estos focos tumorales a los diferentes tratamientos que se usan para el control del cáncer. Aun cuando este es un problema específico fundamental a ser solucionado, ya existen métodos de ensayo inmunohistoquímicos y de biología molecular, que han permitido la ubicación de microfocos de células tumorales en diferentes órganos y tejidos, existiendo diferentes técnicas para determinar y cuantificar estas lesiones. Dentro de estas técnicas destacan la citometría de flujo y diferentes técnicas moleculares que van desde las ya tradicionales hasta las más nuevas y sofisticadas. El objetivo de la presente revisión está dirigido evaluar los nuevos métodos de diagnóstico que permitan la identificación de esta enfermedad residual, lo cual serviría para establecer tratamientos individualizados que pudieran prevenir la recurrencia de la enfermedad en los pacientes de cáncer bajo tratamiento.

Micrometastasis or minimal residual disease has become critically important in oncology since it represents a true clinical problem that must be solved, as the response of these tumor foci to the different treatments that are used for the control of cancer, is still unknown. Even though this is a fundamental specific problem to be solved, there are already immunohistochemical and molecular biology diagnostic methods that have allowed microfoci location of tumor cells in various organs and tissues, and different techniques are available to determine and quantify these lesions. Within these techniques, flow cytometry and different molecular methods are included, and they range from the traditional to the newest and most sophisticated. The goal of this review was aimed to evaluate new diagnostic methods that permit the identification of this residual disease, which would serve to establish individualized treatments and prevent the recurrence of the disease in cancer patients under treatment.