INTRODUCTION

The goal of this workshop is to introduce the student to the rudiments of histopathology of the mammary gland of genetically engineered mice (GEM). The student will be 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 will be illustrated by a slide set of twelve mammary tumors illustrating nine different stains. These sets will be supplemented with this laboratory syllabus, microscopic demonstrations, illustrative e xample images and discussions with the instructor.

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

The slide sets used in this course are from your instructor’s Archives. 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 e xperimental pathologists. They were asked to e xamine 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 e xperienced pathologist with an interest in mammary biology and pathology to ensure careful morphologic evaluation.
  6. NIH should establish a panel of e xperts for review of murine mammary pathobiology so that the necessary degree of e xperience can be developed and disseminated.

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

SLIDE 1

Tissue Identification
(tissue is stained with H&E)

1.1 91-0105(PyMT) 4 x 10 x 20 x 40 x
1.2 95-0368(Myc) 4 x 10 x 20 x 40 x
1.3 95-0004(Myc) 4 x 10 x 20 x 40 x
1.4 97-0597(Neu) 4 x 10 x 20 x 40 x

Pattern

SLIDE 2


Tissue Identification

2.1. 98-0350(Wnt10b) 4 x 10 x 20 x 40 x
2.2. 96-0241(KGF)(Plaque) 4 x 10 x 20 x 40 x
2.3. 99-0868(MTV-Type A tumor) 4 x 10 x 20 x 40 x
2.4. 99-0869(MTV -Type B tumor) 4 x 10 x 20 x 40 x

Pattern

SLIDE 3

Tissue Identification

3.1 99-0984(GSK)(HAN) 4 x 10 x 20 x 40 x
3.2. 98-0964(GSK)(Metastasis) 4 x 10 x 20 x 40 x
3.3. 99-0981(GSK)(Squamous Ca) 4 x 10 x 20 x 40 x
3.4. 99-0981(GSK)(Papillary Ca) 4 x 10 x 20 x 40 x

Pattern