Peter J. Dawson

Malignant MCF10CA1 cell lines derived from premalignant human breast epithelial MCF10AT cells

The MCF10 series of cell lines was derived from benign breast tissue from a woman with fibrocystic disease. The MCF10 human breast epithelial model system consists of mortal MCF10M and MCF10MS (mortal cells grown in serum-free and serum-containing media, respectively), immortalized but otherwise normal MCF10F and MCF10A lines (free-floating versus growth as attached cells), transformed MCF10AneoT cells transfected with T24 Ha-ras, and premalignant MCF10AT cells with potential for neoplastic progression. The MCF10AT, derived from xenograft-passaged MCF10-AneoT cells, generates carcinomas in ∼25% of xenografts. We now report the derivation of fully malignant MCF10CA1 lines that complete the spectrum of progression from relatively normal breast epithelial cells to breast cancer cells capable of metastasis. MCF10CA1 lines display histologic variations ranging from undifferentiated carcinomas, sometimes with focal squamous differentiation, to well-differentiated adenocarcinomas. At least two metastasize to the lung following injection of cells into the tail vein; one line grows very rapidly in the lung, with animals moribund within 4 weeks, whereas the other requires 15 weeks to reach the same endpoint. In addition to variations in efficiency of tumor production, the MCF10CA1 lines show differences in morphology in culture, anchorage-independent growth, karyotype, and immunocytochemistry profiles. The MCF10 model provides a unique tool for the investigation of molecular changes during progression of human breast neoplasia and the generation of tumor heterogeneity on a common genetic background.

Mechanisms of multifocal breast cancer: An immunocytochemical study☆

The issue of whether multifocal breast cancer represents intramammary spread from a single primary tumor or multiple synchronous tumors remains unresolved. We have used a series of immunocytochemical markers, B72.3, DF3, c-erbB-2, SP-1, CEA, and p53, to attempt to answer this question. Of 24 cases with separate discrete synchronous tumors in the same breast, 10 were histologically and immunocytochemically identical, five were histologically similar but immunocytochemically different, two were histologically different but immunocytochemically identical, and in seven cases the tumors were different both histologically and immunocytochemically. In seven of the 24 cases lymph nodes containing metastatic tumor were also available; in each instance, the immunoreactivity of the metastasis was similar to one or other of the tumors in the breast. This study indicates that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors.

Disparate histologic responses in simultaneously resected primary and metastatic osteosarcoma following intravenous neoadjuvant chemotherapy.

Seven patients with newly diagnosed metastatic osteosarcoma underwent simultaneous resection of the primary tumor and metastases following intravenous (IV) neoadjuvant chemotherapy. Histologic response was assessed in all tumor specimens. Disparate responses were noted between primary tumor and metastases and, in some cases, between two or more metastatic tumor deposits. The diverse histologic response to neoadjuvant chemotherapy suggests tumor cell heterogeneity. Changing postoperative therapy on the basis of the histologic response induced in the primary tumor may not be appropriate.

INT2 and ERBB2 amplification and ERBB2 expression in breast tumors from patients with different outcomes

SummaryThe relationships of INT2 and ERBB2 amplification and of ERBB2 overexpression in primary breast tumors to prognostic factors, recurrence, and survival have generated considerable controversy. The rationale for this study is that long-term, recurrence-free survival is a more direct criterion for testing the validity of a tumor marker than correlation either with prognostic factors or with short-term recurrence and survival. We examined the association of recurrence with INT2 and ERBB2 amplification and ERBB2 expression by comparing primary breast tumors from patients surviving without recurrence for ≥ 8.5 years after diagnosis. the LTS group, to tumors from patients recurring within two years, the RR group. The RR (N = 63) and LTS (N = 61) samples were coded and examined for amplification by Southern blotting and for expression by immunohistochemistry. Comparison between the RR and LTS groups demonstrated that INT2 amplification was associated with a significantly (P = 0.018) higher (5.6-fold) risk of recurrence, an association that remained significant after controlling for lymph node (LN), tumor size (TS), and histograde (HG) status. ERBB2 amplification and expression were not associated with a higher recurrence risk. Survival analyses within the RR group, however, demonstrated significantly shorter survival time among cases with than without ERBB2 amplification (P = 0.018, median survival 16 vs 25 months), or ERBB2 expression (P = 0.019, median survival 15 vs 25 months), but not INT2 amplification. Univariate Cox proportional hazards regression models also demonstrated significantly shorter survival among cases with ERBB2 amplification (P = 0.016) or expression (P = 0.049), that remained significant in multivariate analyses (P = 0.022) for ERBB2 amplification. These results indicate a significant positive association between INT2 amplification and risk for tumor recurrence in the RR as compared to the LTS group. The relationship of ERBB2 amplification or overexpression to patient outcome is more complex. ERBB2 amplification and expression have a significant relationship with shorter survival among patients recurrent within two years, but their occurrence in tumors from women surviving without recurrence for ≥ 8.5 years suggests that ERBB2 status is not predictive of shorter survival for all breast cancers.

The original illustrations of Hodgkin's disease

In this report, the illustrations from the original papers on Hodgkins disease are used to trace its early history. Thomas Hodgkins report included six cases of his own and a seventh given to him by Robert Carswell, whose beautiful colored pictures of the latter case accompanied Hodgkins presentation. Early clinical pictures are also presented. The histologic definition of the disease, with its characteristic cell, is traced with drawings from the reports of Greenfield, Sternberg, Reed, and Andrews. Modern histologic and immunocytochemical confirmation (Leu-M1 reactivity) of some of Hodgkins original cases, preserved at Guys Hospital, London, UK, are also illustrated. It is concluded that not only did Hodgkin describe cases of Hodgkins disease that meet present-day criteria, he also included at least one case of non-Hodgkins lymphoma, a term that now might be considered a misnomer.

Massive osteolysis of the chest in children: an unusual cause of respiratory distress.

Massive osteolysis, also called Gorhams disease, is an uncommon disease in which bone virtually disintegrates and is replaced by vascular fibrous connective tissue. The authors treated two children with massive osteolysis of the chest. Both conditions responded well to radiation therapy; one even showed evidence of reossification. Massive osteolysis should be considered in children who have spontaneous hemothorax. The bony structures should be examined for evidence of lytic lesions.

Case report 650

A case is presented in which the conventional radiograph was suggestive of avascular necrosis. This impression remained unchanged inspite of an MRI examination that was more suggestive or replacement of marrow. The diagnosis of ischemic necrosis was strongly supported by the patient having previously established avascular necrosis in the opposite hip. The gross pathologic specimen showed only necrotic tumor, which mimicked avascular necrosis on the plain film. The importance of placing proper confidence in the MRI findings is thus emphasized. A classification and brief description of the various types of chondrosarcoma are included in the Discussion.

A history of cancer of the male breast

Publisher Summary This chapter reviews the history of cancer of the male breast. The twentieth century of the clinical and pathologic features of the disease, the hormonal influences, and genetic factors are discussed. Male breast cancer remains an interesting rarity, which unlike female breast cancer, is not increasing in incidence in the United States. The disease in the two sexes is remarkable for its similarities rather than its differences. These include not only the clinical and morphologic appearances but also tumor markers. While estrogen stimulation, either endogenous or exogenous, may play a role in some cases, it is clear that this is not necessary for breast cancer to develop in men. The association with Kleinfelters syndrome suggests that one or more factors associated with the X chromosome may be involved. The earliest reference to a tumor in the male breast is to be found in Case 45 of the Edwin Smith Surgical Papyrus, which dates from 1600 BC. The discovery of specific breast cancer genes, particularly BRCA2 with its strong association with male breast cancer, makes more likely the hope that the study of breast cancer in men will contribute to the understanding of the much more prevalent cancer in women.