TABLE OF CONTENTS

INTRODUCTION

SLIDE 1

SLIDE 2

SLIDE 3
 
 


INTRODUCTION

This web site is based on the workshop given from October 1 to 5 on Modelling Human Breast Cancer in Mouse at the Jackson Laboratory, Bar Harbor, Maine. The goal of the workshop was to introduce the student to the rudiments of histopathology of the mammary gland of genetically engineered mice (GEM). The subsequent tutorial given on October 7, 1999 at the conference on Modelling Human Breast Cancer in Mouse was modified to meet the needs of the investigators. The student were introduced to the basic techniques, stains and nomenclature of pathology and to the diagnostic schemata recommended by the Annapolis Pathology Panel. The different concepts and terms were illustrated by a slide set of twelve mammary tumors demonstrating nine different stains. These sets were supplemented with this laboratory syllabus, microscopic demonstrations, illustrative example images and discussions with the instructor.

Learning Objectives: As a result of attending and participating in this tutorial and laboratory, the student should be able to dissect that mammary glands of a mouse, sample and prepare lesions properly for fixation, chose the proper fixative, understand the processing techniques used, fill out the synoptic Request Forms, understand the diagnostic terminology of pathology, carry out the basic microscopic examination of their tissues, and interact with the pathologists on their team.

The slide sets used in this course are from your instructor’s Archives. A special thanks is extended to Drs. Muller, Seldin and Leder for generously donating their samples. The recommendations, illustrations, tables and forms were developed with the Annapolis Pathology Panel and will appear in the journal Oncogene in early 2000. The Annapolis Pathology Panel was convened in March and July, 1999. The Annapolis Pathology Panel included three surgical, three veterinary and three experimental pathologists. They were asked to examine the histopathology of GEM mammary glands and to compare the models with human breast cancer. The GEM tumors were found to have; (i) phenotypes similar to those of non-GEM, (ii) signature phenotypes specific to the transgene, and (iii) some morphological similarities to the human disease. The current mouse mammary and human breast tumor classifications describe the majority of GEM lesions but unique morphologic lesions are found in many GEM. Since little information is available on the natural history of GEM lesions, a simple morphologic nomenclature was proposed that allows direct comparisons between models.

The recommendations of the Pathology Panel can be summarized as below:

  1. An interim descriptive morphology-based nomenclature be applied to mammary lesions in mice until sufficient knowledge of their natural history allows a biology based classification system.
  2. The development of a "clinical" classification be deferred until the biology of the atypical intraluminal lesions is more adequately understood.
  3. Detailed comparative studies using ancillary techniques such as immunohistochemistry and in-situ hybridization be undertaken to establish relationships between human and murine cancer.
  4. Standard protocols for the sampling, collection, processing, and reporting of specimens be adopted by the scientific community to ensure more uniform and thorough analysis.
  5. Funding agencies should strongly encourage that research teams studying animal models of disease include an experienced pathologist with an interest in mammary biology and pathology to ensure careful morphologic evaluation.
  6. NIH should establish a panel of experts for review of murine mammary pathobiology so that the necessary degree of experience can be developed and disseminated.

You will be amongst the first to have the opportunity to learn and apply the Annapolis Nomenclature.


THE SLIDE SET

The slide set contains three slides with four samples on each slide. Slide 1 has examples of signature lesions of PyV-mT, myc and erbB2. The four samples allow the student to compare and contrast the different signature lesions. The two examples of myc-type tumors permit observation of different myc tissue patterns while retaining the basic myc type cytology. Slide 2 contains four lesions that are typical of spontaneous tumors induced by MMTV. However, two of the lesions were induced by a transgene rather than the virus. Slide 3 has four examples of GSK mice from Dr. David Seldin showing some patterns typical of transgenic animals and showing the variations sometimes seen in some transgenic systems.

SLIDE 1.
 


 





TISSUE IDENTIFICATION:

1.1 91-0105(PyMT)

1.2 95-0368(Myc)

1.3 95-0004(Myc)

1.4 97-0597(Neu)

PATTERN:

TISSUE IDENTIFICATION:
2.1. 98-0350(Wnt10b)

2.2. 96-0241(KGF)(Plaque)

2.3. 99-0868(MTV-Type A tumor)

2.4. 99-0869(MTV -Type B tumor)

PATTERN:


DESCRIPITION:

DIAGNOSIS

KEYWORDS:

NOTES:
 
 

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TISSUE IDENTIFICATION:

3.1 99-0984(GSK)(HAN)

3.2. 98-0964(GSK)(Metastasis)

3.3. 99-0981(GSK)(Squamous Ca)

3.4. 99-0981(GSK)(Papillary Ca)

PATTERN:

DESCRIPITION:

DIAGNOSIS

KEYWORDS:

NOTES:

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October 9, 1999