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Molecular Oncology, Markers, Clinical Correlates |
Departments of Pathology [M. A. R., M. P., N. M., K. W.] and Internal Medicine [K. J. P., D. C. S., S. K.] and Section of Urology [M. A. R., D. C. S., K. J. P.], University of Michigan, Ann Arbor, Michigan 48109
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ABSTRACT |
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INTRODUCTION |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The term "warm" derives from the short interval between time of death and acquisition of tissue samples during the autopsy. The primary goal of this program was to develop a tumor donor program that would allow men with metastatic hormone-refractory prostate cancer to agree to an immediate autopsy shortly after death. This program would serve as an invaluable resource for molecular and clinical studies on advanced prostate cancer. The following report describes the mechanics and short-term results of this program. Future studies will report on specific scientific projects that have used these materials.
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MATERIALS AND METHODS |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Tissue Procurement Protocol.
Since September 1996, 14 immediate autopsies have been performed at the
University of Michigan Hospitals under the auspices of the Specialized
Program of Research Excellence in Prostate Cancer (NCI Grant CA69568).
These autopsies have been referred to as "warm" or recent autopsies
because of the short time interval between patient death and starting
the necropsy.
When a patient enrolled in this protocol dies, the patient’s family or guardian informs the staff medical oncologist participating in the program. In most cases, the patient was either hospitalized at the time of death or under hospice care. In cases where the patient died outside of the hospital, the body was transported to the University of Michigan Hospitals morgue. Simultaneously, the oncologist assembled the autopsy and tissue procurement teams through a pyramidal notification plan. The autopsy team consisted of a staff genitourinary pathologist, genitourinary pathology fellow, pathology resident, and a pathology assistant. The tissue procurement team consisted of the medical oncologist, staff and postdoctorate researchers, laboratory assistants, and a urology resident. Most all team members were available continuously by pager to assure round-the-clock availability.
On arrival in the morgue, an external examination of the cadaver was performed before spraying the body with ethanol. The pathology team approached the internal organs through an anterior, "Y-shaped" incision, extending from the shoulders to the pubis. The skin and subcutical tissues were retracted from the thorax and abdomen, and the breastplate was removed. The internal organs, from the larynx to the pelvis, were dissected from their posterior attachments to the body, and the diaphragm was freed from its peripheral attachments. While still in continuity with the body, the rectum was cross-clamped to prevent spillage of intestinal contents into the pelvis and abdominal cavities. The dissection was then relinquished to the urology resident.
If the prostate was in place, the urology resident resected the prostate, urinary bladder, and pelvic lymph nodes in a manner similar to that of a cystoprostatectomy. If a previous prostatectomy had been performed, the urology resident removed what pelvic contents remained. This included an evaluation of the pelvic lymph nodes for disease.
After the dissection of the pelvis, the rectum was transected, and the viscera were removed en bloc. The pelvic and the visceral blocks were passed to the pathology team, and primary prostate tumors and sites of metastasis were dissected. Tumor from these sites, as well as unaffected normal tissues, were sprayed with ethanol and harvested by the tissue procurement team under the direction of the staff pathologist. Although most of the tissues were well preserved because of the short interval from death to autopsy, attempts were made to harvest tumors from deep within tissues to further minimize the effects of bacterial contamination and to counter any effects that the alcohol spray may have on tissue culture. Normal and malignant tissues were collected as fresh tissue, snap frozen tissue using liquid nitrogen, and formalin-fixed tissue. A second pathology team removed the calvarium and brain and identified metastases in the skull and dura. The second team also took bone samples from the ribs and vertebral column. Examination for bone metastases was guided by the patient’s bone scan. All suspicious sites by bone scan were sampled. All bone lesions were confirmed by histology. Routinely, samples from multiple ribs, vertebral column, and skull were taken, regardless of bone scan results or presence of gross lesions. This coordinated effort allowed for rapid processing of fresh tissue samples. Histological sections stained with H&E were later prepared from the formalin-fixed, paraffin-embedded tissues to verify its malignant nature. Frozen tissue was stored at -70°C. Fresh tissue was transported to several laboratories for tissue culture experiments. Blood (20–30 ml) was collected in a purple-topped, heparinized tube for extraction of germ-line DNA. Once the tissue harvest was complete, the autopsy proceeded in accordance with the protocol established by the University of Michigan Autopsy Service. This protocol examines all organs (i.e., heart, thyroid, parathyroid, brain, and others) both grossly and microscopically. As standard with all routine autopsies, a detailed provisional and final report are issued by the Department of Pathology.
Organization of Tumor Samples.
Frozen and formalin-fixed, paraffin-embedded tissue samples were kept
in the Specialized Program of Research Excellence tissue core. All
samples are electronically registered using a relational database
(Microsoft Access). This allowed for convenient and rapid access of all
samples.
Establishment of Xenografts.
Using aseptic technique, tumor tissue was harvested from several
metastatic lesions. Special care was taken to avoid areas of necrosis.
For example, when there were multiple metastatic tumors to the liver,
the smaller metastases (2–4 cm) tended to be more viable; the larger
tumors had central tumor necrosis, making them unsuitable for
xenografting. The tumor issue was washed in a solution of HBSS (Life
Technologies, Inc., Gaithersburg, MD) with 5.0% antibiotic/antimycotic
(Life Technologies) at 4°C. Tissue was transferred to 150-mm tissue
culture-treated plastic dishes (Fisher Scientific, Pittsburgh, PA) and
cut into 2–5 mm2 pieces using sterile #20
scalpel blades. Chunks of tumors were bathed on ice in a 1x solution
of Matrigel (Becton Dickinson, Bedford, MA) and transferred to a
laminar flow room housing immune-deficient animals. Nude (athymic) and
SCID3
mice were
briefly anesthetized by Metofane (methoxyflurane; Mallinckrodt
Veterinary, Mundelein, IL) inhalation according to approved protocols.
With scissors, a 5-mm incision was made over the dorso-lumbar
region of each animal, and a cavity was created in the s.c. space using
blunt dissection technique. Tumor pieces were inserted into the
excavation using forceps, and the incision was closed with a sterile
9-mm "autoclip" staple (Fisher Scientific). Animals were monitored
for a postoperative period of 9 months and sacrificed if tumor
negative. Tumors were passaged into new animals every 90–100 days or
when the size reached 3000 mm2 using the above
technique. Tumor tissue was introduced into in vitro tissue
culture as described below.
Cell Culture.
During animal passage, tumor tissue was minced with scalpels and plated
on tissue culture grade 150-mm plastic dishes. Cells were maintained in
a humidified incubator at 37°C with 5.0% CO2.
Initially, media formulations were supplemented with growth factors
presumed to augment the growth of epithelial-like cells. Specifically,
a 1:1 mixture of DMEM/F-12 (Life Technologies) media supplemented with
10 µg/ml epithelial growth factor (Life Technologies), 5 µg/ml
insulin (Sigma Chemical, St. Louis, MO), 10% fetal bovine serum (Life
Technologies), and 1% antibiotic/antimycotic supported the viability
of tumor cells introduced into cell culture. Cells are routinely
passaged every 7 days, and medium was exchanged every 3–4 days. At
least 1–2 million cells per 25-mm flask must be used for viable
passaging.
Determination of PSA Expression.
Conditioned medium was examined for the presence of PSA by Dr. Robert
L. Vessella (University of Washington, Seattle, WA), using an automated
IMx PSA immunoassay system (Abbott Laboratories, Chicago, IL),
according to the manufacturer’s specifications. Confirmation of PSA
expression by the xenografts was performed using formalin-fixed,
paraffin-embedded pieces of xenograft tissue. Monoclonal antibodies for
PSA (DAKO Corp., Carpinteria, CA) were diluted 1:20. Secondary
antibodies were conjugated to biotin, and antigens were detected using
the avidin/biotin complex procedure. All staining was performed using
an automated stainer (Ventana E.S.; Ventana Medical Systems, Tucson,
AZ).
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RESULTS |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The autopsies were performed as outlined in "Materials and
Methods." The median time to autopsy was 2.8 h (range, 1–4.5
h). In most all of the cases performed after 2 h, the delay was
because of transportation of the body from a home or hospice to the
University Hospital. Detailed clinical information regarding the 14
patients is presented in Table 1
and
summarized in Table 2
. The autopsies
revealed widely disseminated prostate tumor in most of the cases (Table 3)
. Some sites, such as the orbit
(case 2), were only examined in some autopsies based on clinical
suspicion. In case 2, the patient had loss of vision in one eye. A
summary of autopsy results presented in Fig. 1
demonstrates the percentage
distribution of prostate cancer for the 14 autopsies. The majority of
cases had prostatic involvement (9 of 10). However, except in 2 cases,
the tumor was seen only focally. Nine of 14 cases had liver metastases,
and these were the largest tumors identified. Eight of 14 cases had
some lymph node involvement. In these cases, chains of lymph nodes were
involved. Periaortic and pulmonary perihilar lymph nodes were two
common sites. Interestingly, pelvic lymph nodes were not involved in
any of the cases. The distribution of bony metastases is presented in
Fig. 2
. Twelve of the 14 cases had some
evidence of bony metastases. The vertebral column, dura, skull, and
ribs were involved in 64% (9 of 14), 43% (6 of 14), 43% (6 of 14),
and 36% (5 of 14) of the cases, respectively. Although the dura is not
a true bony site, these tumors did have underlying bony involvement, as
demonstrated by histological examination. Of interest, one patient with
dural metastases developed a unilateral hearing loss 3 months prior to
death.
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. Care
was taken to remove areas of necrosis. The samples obtained yielded
excellent quality material. This is evidenced by good tumor histology,
immunoreactivity for PSA, and the ability to develop xenografts. At the
microscopic level (Fig. 4)
, little
autolysis was seen. The tumor samples were immunoreactive for PSA (14
of 14 cases; Fig. 4
). Xenografts were successfully established from at
least 8 tumors (Fig. 3D
). There was a success rate of 
5%
for all of the attempted xenografts. Interestingly, this success rate
was unrelated to the postmortem interval. However, it should be noted
that this interval was never >4.5 h. A brief description of the
xenografts and cell lines is presented in Table 4
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DISCUSSION |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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One limitation of any autopsy series is the potential to underestimate the extent of disease. For example, in this present study, metastatic disease to the bone was not seen in 2 of 14 cases. Were these cases really negative? Because the medical oncologists taking care of the patients are involved with the autopsy program, relevant clinical data are known at the time of autopsy. This includes the results of the patient’s bone scan. This information helps guide the team to concentrate on all suspicious areas. In the dissection of the pelvis, an experienced urology resident performed a careful dissection looking for any evidence of pelvic lymph nodes. Therefore, the negative findings for pelvic lymph nodes suggest that local disease was not present, as opposed to a lack of sampling in this area. However, the issue of sampling error cannot be excluded.
Most of the metastatic tumors seen in the current study were growing in sheets of poorly differentiated cells. In the cases where primary tumor was identified, the tumor demonstrated either treatment effect or was poorly differentiated. In all cases, a PSA immunostain was performed to confirm prostatic origin. In cases where the tumor is widely metastatic, it is common to find poorly differentiated tumor. Brawn and Speights (13) looked at 100 autopsies of men with widely metastatic prostate cancer; 70% of tumors were poorly differentiated, and 18% were only focally poorly differentiated. This is in contrast to men with metastatic disease to lymph nodes only; in such cases, 41% were differentiated, and 43% predominantly differentiated. Metastatic tumor identified as an incidental finding in pelvic lymph nodes of men undergoing radical prostatectomy for clinically localized disease demonstrated histologically differentiated disease. In most cases, the prostatic cancer maintained a glandular appearance. Therefore, the type of metastatic prostate cancer identified in the present study has a distinct histological appearance from the early metastases seen in pelvic lymph nodes found incidentally at time of prostatectomy for clinically localized prostate cancer. Yet these tumors still expressed PSA.
The present study provided ample frozen tissue for research purposes. The quality of this material has been excellent, as demonstrated by the ability to grow xenografts. Eight xenografts were developed and have now been serially passaged in mice. Of these eight xenografts, five were developed from bone, two from connective tissue, and one from soft tissue metastatic sites. H&E stain showed them to be consistent with prostatic adenocarcinoma. Histological sections from each xenograft stained positive for PSA. These tumors are a valuable resource to study essentially pure prostate tumor. In addition, because the original tumor (usually metastatic tumor) is available, comparisons can be made with regards to the histology, protein expression, DNA, and RNA.
Xenografts have been extremely helpful in identifying new candidate tumor suppressor genes such as PTEN/MMAC1 (14 , 15) . Novel putative genes involved in prostate cancer have also been identified using xenografts. We are currently isolating and characterizing cell lines from each xenograft, one of which has shown strong evidence of being metastatic to bone in SCID mice. These cell lines may be a valuable addition to existing models of metastatic prostate cancer by providing both in vivo and in vitro model systems developed from the same tissue source. The autopsy study has been particularly useful because of the abundant amount of tumor tissue for potential implantation into SCID or athymic mice. Other samples, such as radical prostatectomy specimens, usually contain only a small amount of tumor; in our institution, cases with grossly recognizable tumor are uncommon.
One great obstacle in developing and maintaining a rapid autopsy program are the resources required to support such an activity. Centers with support from the Specialized Program of Research Excellence or O’Brian programs have been able to maintain vigorous programs. The personnel also need to be available on an on-call basis for the proper functioning of this program. Perhaps most vital to the success of this program is the participation of a clinical oncologist(s), who can recruit potential donors.
The future goal of this program is to continue to recruit men with advanced prostate cancer. By expanding this program, this should make the distribution of these valuable tumor samples and xenografts available to other researchers.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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1 Supported by the Specialized Program of Research
Excellence in Prostate Cancer National Cancer Institute Grant CA69568
and CapCURE 
2 To whom requests for reprints should be
addressed, at Department of Pathology, University of Michigan, 1500
East Medical Center Drive, Room 2G332/Box 0054, Ann Arbor, MI
48109-0054. Phone: (734) 936-6775; Fax: (734)763-4095; E-mail: marubin{at}umich.edu
3 The abbreviations used are: SCID, severe
combined immunodeficient; PSA, prostate-specific antigen.
Received 10/15/99; revised 12/23/99; accepted 12/30/99.
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REFERENCES |
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