Precision Molecular Pathology of Uterine Cancer

Description

This text provides a comprehensive review for practicing pathologists to understand the molecular biology, diagnostics, and predictive markers and implications for therapy of uterine cancer. While molecular based therapeutic strategies for uterine cancer are not as well developed as for some other organ sites, these are the most common gynecologic malignancies and there have been many important recent developments that are discussed in this volume. Comprehensive chapters address essential information about endometrial carcinoma, uterine mesenchymal tumors, and cervical carcinoma and include the pathogenesis of carcinoma and discuss molecular based classification, biomarkers, therapy, prevention, and hereditary cancers of the uterus. Precision Molecular Pathology of Uterine Cancer is a unique and one of a kind resource for practicing pathologists, pathologists in training and gynecologists.

Table of Contents

1. Endometrial Carcinoma: Precursor Lesions and Molecular Profiles
2. Introduction
3. Endometrioid Carcinoma (Type 1)
4. Precursor Lesions
5. Uterine Serous Carcinoma (Type 2)
6. Precursor Lesions
7. Molecular Signature
8. Molecular Alterations in Endometrioid Carcinoma
9. Molecular Alterations in Serous Carcinoma
10. Genomic Characterization of USC
11. Conclusion
12. References
13. Endometrial Carcinoma
14. Classification of Endometrial Carcinoma
15. A Putative Pathogenetic Model for Endometrial Carcinoma
16. Histopathologic Classification
17. Endometrioid Adenocarcinoma
18. Mucinous Carcinoma
19. Serous Carcinoma
20. Clear Cell Carcinoma
21. Mixed Carcinoma
22. Undifferentiated Carcinoma
23. Neuroendocrine Tumors
24. Staging of Endometrial Carcinoma
25. Prognostic Factors
26. Hereditary Endometrial Carcinoma
27. References
28. Immunohistochemical Markers in Endometrial Carcinoma
29. Endometrial Carcinoma Versus Extramüllerian Primaries
30. Endometrial Carcinoma Versus Other Müllerian Primaries
31. Subtyping of Endometrial Carcinoma
32. Endometrial Carcinoma and Lynch Syndrome
33. Acknowledgements
34. References
35. Molecular Pathology of Endometrioid Adenocarcinoma
36. Introduction
37. PI3K/AKT Pathway
38. PTEN
39. PIK3CA
40. PIK3R1 and PIK3R2
41. ARID1A
42. KRAS
43. CTNNB1
44. TP53
45. Microsatellite Instability
46. POLE
47. The Cancer Genome Atlas
48. Acknowledgement
49. References
50. The Molecular Pathology of Serous Endometrial Cancer
51. Introduction
52. Introduction to the Molecular Pathology of SEC
53. TP53 Aberrations in SEC
54. PI3K Pathway Aberrations in SEC
55. PI3K Pathway Aberrations as Therapeutic Targets in SEC
56. HER2 (ERBB2) Aberrations in SEC
57. ΗΕR2 as a Therapeutic Target in SEC
58. FBXW7 Aberrations in SEC
59. PPP2R1A Mutations in SEC
60. CHD4 Mutations in SEC
61. SPOP Mutations in SEC
62. TAF1 Mutations in SEC
63. Novel Clinical Trial Designs
64. Summary and Conclusion
65. References
66. Uterine Clear Cell Carcinoma
67. Introduction
68. Histopathologic Features
69. Immunophenotypic Features
70. Genetic Features
71. Biological Function of Immunohistochemical and Genetic Markers
72. HNF-1β
73. Napsin A
74. Bax and Bcl-2
75. TP53/p53
76. ARID1A/BAF250a
77. PPP2R1A
78. PIK3CA
79. PTEN
80. Precursor Lesion and Oncogenesis
81. Similarity and Differences of Molecular Features of Endometrial and Ovarian Clear Cell Carcinoma
82. Conclusion and Future Directions
83. References
84. Mucinous Adenocarcinoma of the Endometrium
85. Clinical Features
86. Histopathologic Features
87. Immunohistochemical Profile
88. Differential Diagnosis
89. Papillary Mucinous Metaplasia, a Possible Precursor of Mucinous Endometrial Adenocarcinoma
90. Pyloric/Gastric Metaplasia of the Endometrium
91. Genetics
92. KRAS
93. PTEN
94. References
95. Molecular Pathology of Uterine Carcinosarcoma
96. Clinicopathologic Features of Uterine Carcinosarcoma
97. Genetic Alterations
98. p53 Pathway
99. PI3K/AKT Pathway
100. Other Mutated Genes in UCS
101. Mismatch Repair (MMR) Deficiency
102. Copy Number Variations
103. mRNA and miRNA Expression Profiles
104. Molecular Types of UCS
105. Acknowledgements
106. References
107. Hereditary Endometrial Carcinoma
108. Introduction
109. Lynch Syndrome
110. Molecular Basis
111. Clinical Features
112. Pathologic Features
113. Screening and Confirmatory Testing
114. Mismatch Repair Protein Immunohistochemistry
115. Microsatellite Instability Analysis
116. MLH1 Promoter Methylation Analysis
117. DNA Mismatch Repair Gene Mutation Analysis
118. Somatic Gene Mutational Analysis
119. Cowden Syndrome
120. Pathologic Features
121. Molecular Basis
122. Confirmatory Testing
123. Related Syndromes
124. Familial Breast Ovarian Cancer Syndromes (BRCA Mutations)
125. Polymerase Proofreading-(POLD1) Associated Syndrome
126. Li-Fraumeni Syndrome
127. References
128. Targeted Therapy and Prevention of Endometrial Cancer
129. Introduction
130. Introduction to Targeted Therapy for Endometrial Cancer
131. Molecular Landscape of Endometrial Cancer
132. Pathways of Interest in Endometrial Cancer
133. PI3K/AKT Pathway
134. Ras/Raf Pathway
135. Angiogenesis
136. Poly ADP-Ribose Polymerase (PARP) Pathway
137. Epidermal Growth Factor Receptor (EGFR) Pathway
138. Other Agents and Targets of Interest
139. Metformin
140. Dasatinib
141. Angiopoietin (Ang)/Tie-2
142. P53
143. Immune Therapy
144. Prevention of Endometrial Cancer
145. Modifiable Risk Factors
146. Potentially Modifiable Risk Factors
147. Interventions
148. Other Populations for Prevention Strategies
149. Conclusion
150. References
151. Uterine Mesenchymal Tumors
152. Molecular Pathology of Uterine Mesenchymal Tumors
153. Smooth Muscle Tumors
154. Conventional Leiomyoma
155. Cellular Leiomyoma
156. Atypical Leiomyoma
157. Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome
158. Conventional Leiomyosarcoma
159. Unusual Smooth Muscle Neoplasms (“Quasi-malignant”)
160. PEComa
161. Endometrial Stromal Neoplasms
162. Endometrial Stromal Nodule and Low-Grade Endometrial Stromal Sarcoma
163. Recurrent Translocations/Gene Fusions
164. Other Molecular Characterizations of ESN and LGESS
165. High-Grade Endometrial Stromal Sarcoma (HGESS)
166. Other Molecular Features of HGESS
167. Undifferentiated Uterine Sarcoma
168. Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT)
169. Mullerian Adenosarcoma
170. Inflammatory Myofibroblastic Tumor
171. Embryonal Rhabdomyosarcoma
172. Other
173. References
174. Cervical Carcinomas
175. Molecular Pathology of Cervical Dysplasia and Carcinoma
176. Molecular Biology of Cervical Cancer and Precursor Lesions
177. Classification of HPV
178. Natural History of HPV Infection
179. Persistent HPV Infection and Cell Transformation
180. Squamo-Columnar Junction Cells
181. Genetic and Epigenetic Changes in Cervical Cancers
182. Cervical Cancer Prevention and Risk Profiling
183. HPV Testing in Cervical Cancer Prevention
184. HPV and Pap Cytology Co-testing
185. HPV16/18 Genotyping
186. HPV Testing Assays
187. Tumor Markers in Pap Cytology for Cervical Cancer Screening
188. Immunostaining for P16, MIB-1, and MCM2/TOP2A (ProExC) in Pap Cytology Specimens
189. Methylation Markers
190. Molecular Basis of Emerging Biological Treatment for Cervical Cancers
191. Anti-Angiogenic Agents
192. Inhibitors of Epidermal Growth Factor Receptor
193. Inhibitors of the Mammalian Target of Rapamycin
194. Demethylating Agents
195. Proteasome Inhibitors
196. Micro-RNAs and Short Interfering RNAs
197. Antioxidants
198. Cyclooxygenase-2 Inhibitors
199. Anti-viral Agents
200. References
201. Index

Editors Biography

Michael T. Deavers, MDHouston Methodist HospitalPathology and Genomic Medicine Houston, TXUSA
Donna M. Coffey, MDHouston Methodist HospitalPathology and Genomic Medicine Houston, TXUSA