Purpose: Human fibroblast activation protein (FAP)/seprase is a 97-kDa surface glycoprotein expressed on tumor associated fibroblasts in the majority of epithelial cancers including colon adenocarcinomas. FAP overexpression in human tumor cells has been shown to promote tumor growth in animal models, and clinical trials targeting FAP enzymatic activity have been initiated. The primary objective of this study was to evaluate the clinical significance of stromal FAP in human colon cancers by immunohistochemisty. Experimental Design: Sections of paraffin-embedded resected primary human colon cancer specimens from 1996 through 2001 within the Fox Chase Cancer Center tumor bank were stained with D8 antibody directed against FAP/seprase. Xenotransplanted human colorectal tumors in mice were examined similarly for stromal FAP in tumors of different sizes. Overall percentage of stromal FAP staining of the primary tumor was assessed semiquantitatively (0, 1+, 2+, 3+) and staining intensity was also graded (none, weak, intermediate, strong). Survival time and time to recurrence data were analyzed using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. Results: One hundred thirty-eight patients with resected specimens were available for study (mean follow-up, 1,050 days) with 6 (4%) stage I, 52 (38%) stage II, 43 (31%) stage III, and 37 (27%) stage IV patients. FAP was detected in >93% of specimens. Semiquantitative staining was scored as 1+ in 28 (20%), 2+ in 52 (38%), and 3+ in 49 (35%). FAP staining intensity was graded as weak in 45 (33%), intermediate in 48 (35%), and dark in 36 (26%). Stromal FAP was found to correlate inversely with tumor stage (semiquantitative, P = 0.01; intensity, P = 0.009) and with tumor size of the tumor xenograft model (correlation coefficient, À0.61; P = 0.047), suggesting that stromal FAP may have a greater role in the early development of tumors. Furthermore, greater stromal FAP for patients with known metastatic disease was associated with a decreased survival. Conclusion: Our data indicate that patients whose colon tumors have high levels of stromal FAP are more likely to have aggressive disease progression and potential development of metastases or recurrence. This study affirms the rationale for ongoing clinical investigations using FAP as a therapeutic target to disrupt FAP-driven tumor progression in patients with metastatic disease. It also suggests that the effects of FAP inhibition should be investigated in earlier-stage tumors, given its high levels and potential effect earlier in the course of the disease.

Retroperitoneal lesions represent a broad, diverse collection of entities; when they contain fat, the differential diagnosis, which ranges from benign to fully malignant lesions, substantially narrows. Lipomas rarely occur in the retroperitoneum; thus, fat-containing lesions in this location should never be dismissed as lipoma. Pelvic lipomatosis is the overgrowth of histologically normal fat in the extraabdominal compartments of the pelvis along the perirectal and perivesicular spaces. Infants and young children develop lipoblastomas rather than liposarcomas, which occur in older patients. Liposarcomas typically occur in patients 50-70 years old and manifest in multiple subtypes, with the most common being well-differentiated liposarcoma. Liposarcomas are histologically and radiologically protean, with no one imaging feature specific across the spectrum of subtypes. Hibernoma is a rare benign soft-tissue tumor composed of brown fat. Because hibernomas contain varied portions of brown and white fat as well as lesser amounts of myxoid material and spindle cells, their imaging features vary considerably. Teratomas are neoplasms that originate in pluripotent cells--benign or malignant germ cells--that give rise to a wide spectrum of mature or immature tissues that are foreign to the location in which they arise and which demonstrate varying amounts of organ formation. Myelolipoma, a benign tumor composed of mature fat and interspersed hematopoietic elements that resemble bone marrow, typically originate in an otherwise normal adrenal gland. Angiomyolipoma is composed of varying admixtures of blood vessels, smooth muscle cells, and adipose tissue; any one or two of these elements may predominate. Although these fat-containing lesions have overlapping radiologic features, use of demographic and clinical data helps refine the diagnostic options and treatment.

Monitoring response to treatment is a key element in the management of breast cancer that involves several different viewpoints from surgery, radiology, and medical oncology. In the adjuvant setting, appropriate surgical and pathological evaluation guides adjuvant treatment and follow up care focuses on detecting recurrent disease with the intention of improving long term survival. In the neoadjuvant setting, assessing response to chemotherapy prior to surgery to include evaluation for pathologic response can provide prognostic information to help guide follow up care. In the metastatic setting, for those undergoing treatment, it is crucial to determine responders versus non-responders in order to help guide treatment decisions. In this review, we present the current guidelines for monitoring treatment response in the adjuvant, neoadjuvant, and metastatic setting. In addition, we also discuss challenges that are faced in each setting.

Approximately 5-10% of breast cancers may be inheritable, up to 90% of which are due to mutations in BRCA1 and BRCA2. A substantial minority are caused by non-BRCA mutations, such as TP53, PTEN, STK11, CHEK2, ATM, BRIP1, and PALB2 mutations. This review highlights translational research advances with regard to the development of probabilistic models for hereditary breast cancer syndromes, the identification of specific genetic mutations responsible for these syndromes, as well as their testing and interpretations.