Minimal residuale Tumorerkrankung beim Ösophaguskarzinom

Zusammenfassung

Obgleich mikrodisseminierte Tumorzellen in Lymphknoten oder im Knochenmark durch verschiedene Methoden nachgewiesen werden können, ist deren biologische und klinische Relevanz für die Tumorerkrankung nicht restlos geklärt. Die Datenlage hierzu beim Ösophaguskarzinom ist teilweise inkongruent. Letztlich zeigt sich, dass mikrometastatische Tumorzellen in Lymphknoten eine Tumorzellverbreitung repräsentieren, die mit einem signifikant schlechteren Überleben der Patienten verbunden ist und durch das klinisch-pathologische Staging nicht abgebildet wird. Die Wertung von Tumorzellen im Knochenmark ist aufgrund der Heterogenität der Nachweisverfahren und der damit verbundenen diffizilen Validierung insbesondere im Hinblick auf eine klinische Nutzung, z. B. im präoperativen Staging, mit erheblichen Unwägbarkeiten verbunden.

Abstract

Although microdisseminated cancer cells in lymph nodes and in bone marrow can be detected by a variety of methods, their biological and clinical relevance remains unclear. The following article focusing on minimal residual disease in esophageal cancer illustrates and debates numerous publications with reference to this issue. In conclusion, micometastatic cancer cells in lymph nodes indicate systemic spread of disease not reflected by conventional clinical and histological staging, hereby resulting in significantly impaired survival of patients. The detection of cancer cells in bone marrow is clouded by the heterogeneity of their analytic assessment. Consequently, its diagnostic validity seems to be arguable in terms of introduction into clinical practice, e. g. preoperative staging.

Schlüsselwörter

minimal residuale Tumorerkrankung - Mikrometastasen - Mikrodisseminierung - Ösophaguskarzinom - Staging

Key words

minimal residual disease - micrometastasis - micodissemination - esophageal cancer - staging

Literatur

• 1 Gearhart P J, Sigal N H, Klinman N R. Production of antibodies of identical idiotype but diverse immunoglobulin classes by cells derived from a single stimulated B cell.  Proc Natl Acad Sci U S A. 1975;  72 1707-1711
• 2 Fisher E R, Swamidoss S, Lee C H, Rockette H, Redmond C, Fisher B. Detection and significance of occult axillary node metastases in patients with invasive breast cancer.  Cancer. 1978;  42 2025-2031
• 3 Pickren J W. Significance of occult metastases. A study of breast cancer.  Cancer. 1961;  14 1266-1271
• 4 Friedman S, Bertin F, Mouriesse H. et al . Importance of tumor cells in axillary node sinus margins (‘clandestine’ metastases) discovered by serial sectioning in operable breast carcinoma.  Acta Oncol. 1988;  27 483-487
• 5 Rosen P P, Saigo P E, Braun D W, Weathers E, Fracchia A A, Kinne D W. Axillary micro- and macrometastases in breast cancer: prognostic significance of tumor size.  Ann Surg. 1981;  194 585-591
• 6 Yoshinaka H, Shimazu H, Natsugoe S. et al . [Histopathological features of the lymph node metastases in patients with thoracic esophageal cancer].  Nippon Geka Gakkai Zasshi. 1992;  93 1289-1296
• 7 Komukai S, Nishimaki T, Watanabe H, Ajioka Y, Suzuki T, Hatakeyama K. Significance of immunohistochemically demonstrated micrometastases to lymph nodes in esophageal cancer with histologically negative nodes.  Surgery. 2000;  127 40-46
• 8 International (Ludwig) Breast Cancer Study Group . Prognostic importance of occult axillary lymph node micrometastases from breast cancers.  Lancet. 1990;  335 1565-1568
• 9 Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H. Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial.  J Clin Pathol. 1990;  43 213-219
• 10 Passlick B, Izbicki J R, Kubuschok B. et al . Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer.  J Clin Oncol. 1994;  12 1827-1832
• 11 Byrne J, Waldron R, McAvinchey D, Dervan P. The use of monoclonal antibodies for the histopathological detection of mammary axillary micrometastases.  Eur J Surg Oncol. 1987;  13 409-411
• 12 Bussolati G, Gugliotta P, Morra I, Pietribiasi F, Berardengo E. The immunohistochemical detection of lymph node metastases from infiltrating lobular carcinoma of the breast.  Br J Cancer. 1986;  54 631-636
• 13 Stahel R A, Mabry M, Skarin A T, Speak J, Bernal S D. Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody.  J Clin Oncol. 1985;  3 455-461
• 14 Redding W H, Coombes R C, Monaghan P. et al . Detection of micrometastases in patients with primary breast cancer.  Lancet. 1983;  2 1271-1274
• 15 Coombes R C, Dearnaley D P, Buckman R. et al . Detection of bone metastases in patients with breast cancer.  Invasion Metastasis. 1982;  2 177-184
• 16 Schlimok G, Funke I, Holzmann B. et al . Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies.  Proc Natl Acad Sci USA. 1987;  84 8672-8676
• 17 Ross A A, Miller G W, Moss T J. et al . Immunocytochemical detection of tumor cells in bone marrow and peripheral blood stem cell collections from patients with ovarian cancer.  Bone Marrow Transplant. 1995;  15 929-933
• 18 Hay F G, Ford A, Leonard R C. Clinical applications of immunocytochemistry in the monitoring of the bone marrow in small cell lung cancer (SCLC).  Int J Cancer Suppl. 1988;  2 8-10
• 19 Deguchi T, Yang M, Ehara H. et al . Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.  Br J Cancer. 1997;  75 634-638
• 20 Pecorini F, Veneziano M, Framarino Dei Malatesta M L. et al . Considerations on the prognostic significance of bone marrow micrometastases in breast cancer.  Eur J Gynaecol Oncol. 1993;  14 501-505
• 21 Izbicki J R, Hosch S B, Pichlmeier U. et al . Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer.  N Engl J Med. 1997;  337 1188-1194
• 22 Heiss M M, Allgayer H, Gruetzner K U, Babic R, Jauch K W, Schildberg F W. Clinical value of extended biologic staging by bone marrow micrometastases and tumor-associated proteases in gastric cancer.  Ann Surg. 1997;  226 736-744
• 23 Neville A M. Breast cancer micrometastases in lymph nodes and bone marrow are prognostically important.  Ann Oncol. 1991;  2 13-14
• 24 Untch M, Harbeck N, Eiermann W. [Micrometastases in bone marrow at the time of primary treatment of breast cancer: a new prognostic criterion?].  Gynakol Rundsch. 1989;  29 (Suppl 2) 231-233
• 25 Passlick B, Izbicki J R, Kubuschok B, Thetter O, Pantel K. Detection of disseminated lung cancer cells in lymph nodes: impact on staging and prognosis.  Ann Thorac Surg. 1996;  61 177-182
• 26 Izbicki J R, Hosch S B. Minimal dissemination of solid epithelial tumours: impact on staging and therapeutic strategy.  Br J Surg. 1997;  84 897-898
• 27 Pantel K, Cote R J, Fodstad O. Detection and clinical importance of micrometastatic disease.  J Natl Cancer Inst. 1999;  91 1113-1124
• 28 Relihan N, McGreal G, Kelly J, Ryan D, O'Sullivan G C, Redmond H P. Combined sentinel lymph-node mapping and bone-marrow micrometastatic analysis for improved staging in breast cancer.  Lancet. 1999;  354 129-130
• 29 Lerut T, De Leyn P, Coosemans W, Van Raemdonck D, Scheys I, LeSaffre E. Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy.  Ann Surg. 1992;  216 583-590
• 30 Hulscher J B, van Sandick J W, de Boer A G. et al . Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus.  N Engl J Med. 2002;  347 1662-1669
• 31 Stein H J, Siewert J R. Improved prognosis of resected esophageal cancer.  World J Surg. 2004;  28 520-525
• 32 Veronesi U, Galimberti V, Mariani L. et al . Sentinel node biopsy in breast cancer: early results in 953 patients with negative sentinel node biopsy and no axillary dissection.  Eur J Cancer. 2005;  41 231-237
• 33 Kapteijn B A, Nieweg O E, Petersen J L. et al . Identification and biopsy of the sentinel lymph node in breast cancer.  Eur J Surg Oncol. 1998;  24 427-430
• 34 Albertini J J, Cruse C W, Rapaport D. et al . Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma.  Ann Surg. 1996;  223 217-224
• 35 Yoshino I, Yokoyama H, Yano T. et al . Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer.  Ann Thorac Surg. 1996;  62 1021-1025
• 36 Ducci M, Appetecchia M, Marzetti M. Neck dissection for surgical treatment of lymphnode metastasis in papillary thyroid carcinoma.  J Exp Clin Cancer Res. 1997;  16 33-335
• 37 Hosch S B, Stoecklein N H, Pichlmeier U. et al . Esophageal cancer: the mode of lymphatic tumor cell spread and its prognostic significance.  J Clin Oncol. 2001;  19 1970-1975
• 38 Natsugoe S, Mueller J, Stein H J, Feith M, Hofler H, Siewert J R. Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis.  Cancer. 1998;  83 858-866
• 39 Mueller J D, Stein H J, Oyang T. et al . Frequency and clinical impact of lymph node micrometastasis and tumor cell microinvolvement in patients with adenocarcinoma of the esophagogastric junction.  Cancer. 2000;  89 1874-1882
• 40 Greenson J K, Isenhart C E, Rice R, Mojzisik C, Houchens D, Martin E W. Identification of occult micrometastases in pericolic lymph nodes of Duke's B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival.  Cancer. 1994;  73 563-569
• 41 Trojani M, de Mascarel I, Bonichon F, Coindre J M, Delsol G. Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance.  Br J Cancer. 1987;  55 303-306
• 42 Hosch S B, Knoefel W T, Metz S. et al . Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and prognostic significance.  Pancreas. 1997;  15 154-159
• 43 Sakata K. Ueber die Lymphgefässe des: Oesophagus und über seine regionären Lymphdrüsen mit Berücksichtigung der Verbreitung des Carcinoms.  Mitt Grenzgeb Medizin. 1903;  11 629-656
• 44 Junker K, Gumprich T, Muller K M. [Discontinuous lymph node metastases (“skipping”) in malignant lung tumors].  Chirurg. 1997;  68 596-599
• 45 van de Ven C, De Leyn P, Coosemans W, Van Raemdonck D, Lerut T. Three-field lymphadenectomy and pattern of lymph node spread in T3 adenocarcinoma of the distal esophagus and the gastro-esophageal junction.  Eur J Cardiothorac Surg. 1999;  15 769-773
• 46 Akiyama H, Tsurumaru M, Kawamura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus: analysis of lymph node involvement.  Ann Surg. 1981;  194 438-446
• 47 Zgajnar J, Besic N, Podkrajsek M, Hertl K, Frkovic-Grazio S, Hocevar M. Minimal risk of macrometastases in the non-sentinel axillary lymph nodes in breast cancer patients with micrometastatic sentinel lymph nodes and preoperatively ultrasonically uninvolved axillary lymph nodes.  Eur J Cancer. 2005;  41 244-248
• 48 Wong S L, Kattan M W, McMasters K M, Coit D G. A nomogram that predicts the presence of sentinel node metastasis in melanoma with better discrimination than the American Joint Committee on Cancer staging system.  Ann Surg Oncol. 2005;  12 282-288
• 49 Lamb P J, Griffin S M, Burt A D, Lloyd J, Karat D, Hayes N. Sentinel node biopsy to evaluate the metastatic dissemination of oesophageal adenocarcinoma.  Br J Surg. 2005;  92 60-67
• 50 Nomura T, Onda M, Miyashita M. et al . Wide-spread distribution of sentinel lymph nodes in esophageal cancer.  J Nippon Med Sch. 2001;  68 393-396
• 51 Matsubara T, Ueda M, Kaisaki S. et al . Localization of initial lymph node metastasis from carcinoma of the thoracic esophagus.  Cancer. 2000;  89 1869-1873
• 52 Kitagawa Y, Fujii H, Mukai M. et al . [The validity of the sentinel node concept in gastrointestinal cancers].  Nippon Geka Gakkai Zasshi. 2000;  101 315-319
• 53 Kato H, Miyazaki T, Nakajima M. et al . Sentinel lymph nodes with technetium-99m colloidal rhenium sulfide in patients with esophageal carcinoma.  Cancer. 2003;  98 932-939
• 54 Yasuda S, Shimada H, Chino O. et al . Sentinel lymph node detection with ^99mTc tin colloids in patients with esophagogastric cancer.  Jpn J Clin Oncol. 2003;  33 68-72
• 55 Braun S, Pantel K. Micrometastatic bone marrow involvement: detection and prognostic significance.  Med Oncol. 1999;  16 154-165
• 56 Inoue H, Kajiyama Y, Tsurumaru M. Clinical significance of bone marrow micrometastases in esophageal cancer.  Dis Esophagus. 2004;  17 328-332
• 57 Bonavina L, Soligo D, Quirici N. et al . Bone marrow-disseminated tumor cells in patients with carcinoma of the esophagus or cardia.  Surgery. 2001;  129 15-22