TISSUE IS THE ISSUE—2023 Update on AIM’s International Melanoma Tissue Bank Consortium

Published:  
01/26/2023
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This article is an update of an article we published last year.

AIM at Melanoma’s major research initiative—the International Melanoma Tissue Bank Consortium (IMTBC)—is the first of its kind in the world. Currently comprising four sites in the U.S. (with two Australian sites to be added), the IMTBC is a resource of primary melanoma tumor tissues and data for use by the participating institutions’ researchers as well as researchers around the world who can apply to use the tissue/data.

As we noted last year, COVID hit research projects like this hard, as only “essential” medical appointments were scheduled during the pandemic. And since then, offices and patients have been slowly getting back to normal. As you’ll read below, the typical way we collect a primary tumor tissue is at one of four research institutions during a skin check appointment. Since these institutions are also major hospitals, getting back to normal has been complicated because COVID affected hospitals in a much different way than it did independent physician offices. But we are moving in the right direction, and collection resumed and continued at all four U.S. sites in 2022. As of the end of the 3rd quarter (September 30, 2022) reporting, we have collected 110 fresh frozen primary tissues and corresponding data.

The following is an FAQ about the tissue bank. Some of the questions we’ve published previously; some are new.

¿Qué es el banco de tejidos? ¿Es un edificio real?

The IMTBC is not a building. It operates within certain existing medical centers. Dermatologists, surgeons, oncologists, pathologists, and other staff all participate in creating the bank at a participating cancer center.

¿Cómo funciona?

Así es como funciona normalmente: Un paciente acude a su dermatólogo para una revisión de la piel en una de las sedes del banco de tejidos. El médico encuentra una lesión sospechosa de melanoma y tiene la intención de hacerle una biopsia. Antes de comenzar la escisión, el médico pide el consentimiento del paciente para utilizar parte del tejido y la información médica del paciente -personalizada- para la investigación. Si se concede, se extrae una parte del tejido para la biopsia y se congela inmediatamente otra parte, lo que, críticamente, preserva el ARN. El médico también pide al paciente que rellene un cuestionario especial y recoge otras muestras, como sangre. El personal introduce el historial médico del paciente y las respuestas al cuestionario (de nuevo, todo despersonalizado) en una base de datos especial, y las muestras y el tejido se codifican y almacenan en frigoríficos/congeladores.

The bank, then, is made up of both fresh frozen tumor tissue and other samples, such as blood, as well as data about each patient.

What will the researchers do with the tissue and accompanying patient information?

Once a critical mass of tissues and data are collected from a variety of patients, the researchers can look at these fresh frozen primary melanomas and the accompanying data to find medical signs or indications, called biomarkers, that are shared by some or all of the tissues. These biomarkers will help reveal insights into diagnosis, prognosis, and treatment.

Please read this article for even more information.

Can I participate?

This question is the most common one we get.

At this time, only certain people can participate, and they likely won’t be anyone who is reading this article. Why? Remember that we are collecting primary melanoma tumor tissue—primary means the original melanoma found on your body, the one that was deemed Stage I or Stage II. Those who are reading an article like this are probably long past that original biopsy—though they may be able to participate if they have a second primary melanoma. Further, the patient needs to be seen at one of our tissue bank sites at Hillman Cancer Center, University of Pittsburgh Medical Center (Pittsburgh, PA); Knight Cancer Institute, Oregon Health and Science University (Portland, OR); California Pacific Medical Center (San Francisco, CA); or Robert H. Lurie Comprehensive Cancer Center, Northwestern University (Chicago, IL). Finally, the suspected melanoma must be large enough to bank.

So ironically, it is people likely unfamiliar with the melanoma world and melanoma research—because at the time of the biopsy, they won’t even know if they have melanoma—whose information and samples will populate this bank and help researchers understand melanoma better.

Esperamos contar en el futuro con más lugares en Estados Unidos para poder recoger más tejido primario, pero por ahora nos limitamos a recoger en los cuatro lugares estadounidenses mencionados.

¿Por qué el IMTBC es único?

IMTBC is a global first because of the following combination of factors:

  • Es un consorcio: los investigadores de las instituciones comparten datos y muestras de tejido entre sí
  • Se trata de una colaboración: las muestras y los datos de los tejidos estarán disponibles para que los investigadores de todo el mundo los soliciten para estudiar
  • The tissue is fresh frozen—RNA is preserved, unlike in the standard formalin fixed, paraffin embedded process
  • Los tumores son primarios, no metastásicos
  • Habrá una masa crítica, un objetivo de 500 para empezar, y una recogida continua después
  • Full annotation will accompany each tissue—patient data, including full medical history (depersonalized), will be available for study along with the tissue
  • Samples accompany each tissue—blood and other samples are collected for each patient

Why is fresh frozen tissue important?

Formalin-fixed, paraffin imbedded is the standard way of storing primary tumors. In this method, a lot of water is depleted from the tissue, which degrades the proteins. The messenger RNA is also degraded into smaller pieces during the fixing process, and researchers want the messenger RNA intact. Fresh frozen tissue preserves RNA. Finally, a tumor cell has already initiated an immune response, and researchers are able to recognize that in a fresh frozen piece but not in a formalin-fixed piece.

Why is primary tumor tissue important?

La información del tumor primario es importante porque es fija. La heterogeneidad de la enfermedad sólo puede leerse en el tumor primario: es el mejor lugar para entender la heterogeneidad de la enfermedad. Hay una enorme cantidad de información en el tumor primario que puede ayudarnos a predecir el futuro del paciente si podemos aprender a leerlo. El tumor primario contiene TODA la información sobre la enfermedad.

The highest degree of genetic alterations is found in the primary tumor.  During the course of the disease, the tumor loses large DNA fragments.  For research, you want to look at the tumor at several “time points,” if possible, starting most importantly with the primary tumor.

Si vamos a encontrar marcadores predictivos o pronósticos, será en el tumor primario.

By contrast, metastasized tumors are a product of the organ in which they are growing, and they will reflect that organ. Some tumor cells go to the lymph nodes, and other cells go into the bloodstream, so you don’t get a full picture of the person’s disease from the metastases.

If primary melanoma tissue that is fresh frozen is so important for research, why isn’t there more available?

Una de las razones es que el tejido fresco congelado del melanoma primario no puede recogerse y congelarse en la consulta típica del dermatólogo, y en la consulta típica del dermatólogo es donde se realizan la mayoría de las biopsias de melanoma. La mayoría de las consultas de dermatología no cuentan con un patólogo interno, por lo que el dermatólogo debe enviar físicamente sus biopsias a una consulta de patología externa. Esta situación elimina la posibilidad de separar con seguridad una parte de la muestra y congelarla para la investigación sin comprometer el diagnóstico, especialmente si el melanoma es pequeño. Incluso cuando la consulta de un dermatólogo cuenta con un patólogo interno, la mayoría de las consultas de dermatología/patología no disponen del tiempo, la instalación o todos los materiales necesarios para congelar rápidamente el tejido (utilizando nitrógeno líquido) o almacenarlo (los congeladores de nitrógeno líquido funcionan a una temperatura de -140°C a -196°C). Además, parte de las muestras deben procesarse inmediatamente, lo que requiere un laboratorio in situ, del que no se dispone en una clínica dermatológica típica. Y ninguna de las dificultades anteriores incluye los complicadísimos procedimientos y normas en torno a la obtención del consentimiento de los pacientes para la recogida de tejidos y el uso de esos tejidos para la investigación; una vez más, una consulta de dermatología típica no trabaja en este ámbito.

Dermatology offices located at research institutions, however, with on-site pathology offices and on site laboratories and appropriate space and equipment, are the places that can successfully separate, freeze, and store fresh frozen primary tissue for research. But even these places need to be organized, managed, and paid to consent patients appropriately; to put the collection processes in place; to label and store tissue; and to oversee the use of the tissue by internal and external researchers. This organization, management, and funding are what IMTBC has successfully accomplished.

What happens next?

Critical mass is important. We are at 110 tissues, and the site researchers wanted 100 tissues at the very least to begin their research—the more tissues, the more that can be revealed through their studies—so this year, we should see the first research project(s) using the tissue.

We are in initial conversation with another U.S. institution to join the consortium, and we are in continued conversation with our Australian sites on the “how” of collection, collaboration, and processes and hope that they can officially open soon. We will announce any and all news as it happens!